共 183 条
mRNA capping: biological functions and applications
被引:592
作者:

Ramanathan, Anand
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机构:
New England Biolabs Inc, 240 Cty Rd, Ipswich, MA 01938 USA
Agios Pharmaceut, 88 Sidney St, Cambridge, MA 02139 USA New England Biolabs Inc, 240 Cty Rd, Ipswich, MA 01938 USA

Robb, G. Brett
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New England Biolabs Inc, 240 Cty Rd, Ipswich, MA 01938 USA New England Biolabs Inc, 240 Cty Rd, Ipswich, MA 01938 USA

Chan, Siu-Hong
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h-index: 0
机构:
New England Biolabs Inc, 240 Cty Rd, Ipswich, MA 01938 USA New England Biolabs Inc, 240 Cty Rd, Ipswich, MA 01938 USA
机构:
[1] New England Biolabs Inc, 240 Cty Rd, Ipswich, MA 01938 USA
[2] Agios Pharmaceut, 88 Sidney St, Cambridge, MA 02139 USA
关键词:
CAP-BINDING COMPLEX;
VESICULAR STOMATITIS-VIRUS;
RECEPTOR RIG-I;
25-KDA THIAMINE TRIPHOSPHATASE;
QUALITY-CONTROL MECHANISM;
CARBOXY-TERMINAL DOMAIN;
CENTRAL-NERVOUS-SYSTEM;
IFIT FAMILY-MEMBERS;
BLUETONGUE VIRUS;
STRUCTURAL BASIS;
D O I:
10.1093/nar/gkw551
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
The 5' m7G cap is an evolutionarily conserved modification of eukaryotic mRNA. Decades of research have established that the m7G cap serves as a unique molecular module that recruits cellular proteins and mediates cap-related biological functions such as pre-mRNA processing, nuclear export and cap-dependent protein synthesis. Only recently has the role of the cap 2'O methylation as an identifier of self RNA in the innate immune system against foreign RNA has become clear. The discovery of the cytoplasmic capping machinery suggests a novel level of control network. These new findings underscore the importance of a proper cap structure in the synthesis of functional messenger RNA. In this review, we will summarize the current knowledge of the biological roles of mRNA caps in eukaryotic cells. We will also discuss different means that viruses and their host cells use to cap their RNA and the application of these capping machineries to synthesize functional mRNA. Novel applications of RNA capping enzymes in the discovery of new RNA species and sequencing the microbiome transcriptome will also be discussed. We will end with a summary of novel findings in RNA capping and the questions these findings pose.
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页码:7511 / 7526
页数:16
相关论文
共 183 条
[31]
The pioneer translation initiation complex is functionally distinct from but structurally overlaps with the steady-state translation initiation complex
[J].
Chin, SY
;
Lejeune, F
;
Ranganathan, AC
;
Maquat, LE
.
GENES & DEVELOPMENT,
2004, 18 (07)
:745-754

Chin, SY
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Rochester, Sch Med & Dent, Dept Biochem & Biophys, Rochester, NY 14642 USA Univ Rochester, Sch Med & Dent, Dept Biochem & Biophys, Rochester, NY 14642 USA

论文数: 引用数:
h-index:
机构:

Ranganathan, AC
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Rochester, Sch Med & Dent, Dept Biochem & Biophys, Rochester, NY 14642 USA Univ Rochester, Sch Med & Dent, Dept Biochem & Biophys, Rochester, NY 14642 USA

Maquat, LE
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Rochester, Sch Med & Dent, Dept Biochem & Biophys, Rochester, NY 14642 USA Univ Rochester, Sch Med & Dent, Dept Biochem & Biophys, Rochester, NY 14642 USA
[32]
mRNA capping enzyme is recruited to the transcription complex by phosphorylation of the RNA polymerase II carboxy-terminal domain
[J].
Cho, EJ
;
Takagi, T
;
Moore, CR
;
Buratowski, S
.
GENES & DEVELOPMENT,
1997, 11 (24)
:3319-3326

Cho, EJ
论文数: 0 引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

Takagi, T
论文数: 0 引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

Moore, CR
论文数: 0 引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

Buratowski, S
论文数: 0 引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA
[33]
eIF4AIII enhances translation of nuclear cap-binding complex-bound mRNAs by promoting disruption of secondary structures in 5′UTR
[J].
Choe, Junho
;
Ryu, Incheol
;
Park, Ok Hyun
;
Park, Joori
;
Cho, Hana
;
Yoo, Jin Seon
;
Chi, Sung Wook
;
Kim, Min Kyung
;
Song, Hyun Kyu
;
Kim, Yoon Ki
.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,
2014, 111 (43)
:E4577-E4586

Choe, Junho
论文数: 0 引用数: 0
h-index: 0
机构:
Korea Univ, Div Life Sci, Seoul 136701, South Korea Korea Univ, Div Life Sci, Seoul 136701, South Korea

论文数: 引用数:
h-index:
机构:

Park, Ok Hyun
论文数: 0 引用数: 0
h-index: 0
机构:
Korea Univ, Div Life Sci, Seoul 136701, South Korea Korea Univ, Div Life Sci, Seoul 136701, South Korea

论文数: 引用数:
h-index:
机构:

论文数: 引用数:
h-index:
机构:

Yoo, Jin Seon
论文数: 0 引用数: 0
h-index: 0
机构:
Sungkyunkwan Univ, Samsung Adv Inst Hlth Sci & Technol, Dept Hlth Sci & Technol, Seoul 135710, South Korea Korea Univ, Div Life Sci, Seoul 136701, South Korea

Chi, Sung Wook
论文数: 0 引用数: 0
h-index: 0
机构:
Sungkyunkwan Univ, Samsung Adv Inst Hlth Sci & Technol, Dept Hlth Sci & Technol, Seoul 135710, South Korea
Samsung Res Inst Future Med, Samsung Med Ctr, Seoul 135710, South Korea Korea Univ, Div Life Sci, Seoul 136701, South Korea

论文数: 引用数:
h-index:
机构:

论文数: 引用数:
h-index:
机构:

论文数: 引用数:
h-index:
机构:
[34]
Translation Initiation on mRNAs Bound by Nuclear Cap-binding Protein Complex CBP80/20 Requires Interaction between CBP80/20-dependent Translation Initiation Factor and Eukaryotic Translation Initiation Factor 3g
[J].
Choe, Junho
;
Oh, Nara
;
Park, Sungjin
;
Lee, Ye Kyung
;
Song, Ok-Kyu
;
Locker, Nicolas
;
Chi, Sung-Gil
;
Kim, Yoon Ki
.
JOURNAL OF BIOLOGICAL CHEMISTRY,
2012, 287 (22)
:18500-18509

Choe, Junho
论文数: 0 引用数: 0
h-index: 0
机构:
Korea Univ, Sch Life Sci & Biotechnol, Seoul 136701, South Korea Korea Univ, Sch Life Sci & Biotechnol, Seoul 136701, South Korea

Oh, Nara
论文数: 0 引用数: 0
h-index: 0
机构:
Korea Univ, Sch Life Sci & Biotechnol, Seoul 136701, South Korea Korea Univ, Sch Life Sci & Biotechnol, Seoul 136701, South Korea

Park, Sungjin
论文数: 0 引用数: 0
h-index: 0
机构:
Korea Univ, Sch Life Sci & Biotechnol, Seoul 136701, South Korea Korea Univ, Sch Life Sci & Biotechnol, Seoul 136701, South Korea

Lee, Ye Kyung
论文数: 0 引用数: 0
h-index: 0
机构:
Panbionet Corp, Pohang 790784, Kyungbuk, South Korea Korea Univ, Sch Life Sci & Biotechnol, Seoul 136701, South Korea

Song, Ok-Kyu
论文数: 0 引用数: 0
h-index: 0
机构:
Panbionet Corp, Pohang 790784, Kyungbuk, South Korea Korea Univ, Sch Life Sci & Biotechnol, Seoul 136701, South Korea

Locker, Nicolas
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Surrey, Dept Microbial & Cellular Sci, Guildford GU2 7HX, Surrey, England Korea Univ, Sch Life Sci & Biotechnol, Seoul 136701, South Korea

Chi, Sung-Gil
论文数: 0 引用数: 0
h-index: 0
机构:
Korea Univ, Sch Life Sci & Biotechnol, Seoul 136701, South Korea Korea Univ, Sch Life Sci & Biotechnol, Seoul 136701, South Korea

论文数: 引用数:
h-index:
机构:
[35]
Structure of the guanylyltransferase domain of human mRNA capping enzyme
[J].
Chu, Chun
;
Das, Kalyan
;
Tyminski, James R.
;
Bauman, Joseph D.
;
Guan, Rongjin
;
Qiu, Weihua
;
Montelione, Gaetano T.
;
Arnold, Eddy
;
Shatkin, Aaron J.
.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,
2011, 108 (25)
:10104-10108

Chu, Chun
论文数: 0 引用数: 0
h-index: 0
机构:
Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA
Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Mol Genet Microbiol & Immunol, Piscataway, NJ 08854 USA Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA

Das, Kalyan
论文数: 0 引用数: 0
h-index: 0
机构:
Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA
Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA

Tyminski, James R.
论文数: 0 引用数: 0
h-index: 0
机构:
Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA
Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA

Bauman, Joseph D.
论文数: 0 引用数: 0
h-index: 0
机构:
Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA
Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA

Guan, Rongjin
论文数: 0 引用数: 0
h-index: 0
机构:
Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA
Rutgers State Univ, Dept Mol Biol & Biochem, Piscataway, NJ 08854 USA Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA

Qiu, Weihua
论文数: 0 引用数: 0
h-index: 0
机构:
Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA
Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Mol Genet Microbiol & Immunol, Piscataway, NJ 08854 USA Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA

Montelione, Gaetano T.
论文数: 0 引用数: 0
h-index: 0
机构:
Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA
Rutgers State Univ, Dept Mol Biol & Biochem, Piscataway, NJ 08854 USA Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA

Arnold, Eddy
论文数: 0 引用数: 0
h-index: 0
机构:
Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA
Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA

Shatkin, Aaron J.
论文数: 0 引用数: 0
h-index: 0
机构:
Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA
Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Mol Genet Microbiol & Immunol, Piscataway, NJ 08854 USA Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA
[36]
Specific regulation of mRNA cap methylation by the c-Myc and E2F1 transcription factors
[J].
Cole, M. D.
;
Cowling, V. H.
.
ONCOGENE,
2009, 28 (09)
:1169-1175

Cole, M. D.
论文数: 0 引用数: 0
h-index: 0
机构:
Dartmouth Med Sch, Dept Pharmacol, Lebanon, NH USA
Dartmouth Med Sch, Dept Genet, Lebanon, NH USA Univ Dundee, Coll Life Sci, Div Cell Biol & Immunol, Dundee DD1 5EH, Scotland

Cowling, V. H.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Dundee, Coll Life Sci, Div Cell Biol & Immunol, Dundee DD1 5EH, Scotland Univ Dundee, Coll Life Sci, Div Cell Biol & Immunol, Dundee DD1 5EH, Scotland
[37]
The Bin3 RNA methyltransferase targets 7SK RNA to control transcription and translation
[J].
Cosgrove, Michael S.
;
Ding, Ye
;
Rennie, William A.
;
Lane, Michael J.
;
Hanes, Steven D.
.
WILEY INTERDISCIPLINARY REVIEWS-RNA,
2012, 3 (05)
:633-647

Cosgrove, Michael S.
论文数: 0 引用数: 0
h-index: 0
机构:
SUNY Upstate Med Univ, Dept Biochem & Mol Biol, Syracuse, NY USA SUNY Upstate Med Univ, Dept Biochem & Mol Biol, Syracuse, NY USA

Ding, Ye
论文数: 0 引用数: 0
h-index: 0
机构:
New York State Dept Hlth, Wadsworth Ctr, Ctr Med Sci, Albany, NY USA SUNY Upstate Med Univ, Dept Biochem & Mol Biol, Syracuse, NY USA

Rennie, William A.
论文数: 0 引用数: 0
h-index: 0
机构:
New York State Dept Hlth, Wadsworth Ctr, Ctr Med Sci, Albany, NY USA SUNY Upstate Med Univ, Dept Biochem & Mol Biol, Syracuse, NY USA

Lane, Michael J.
论文数: 0 引用数: 0
h-index: 0
机构:
SUNY Upstate Med Univ, Dept Med, Syracuse, NY USA SUNY Upstate Med Univ, Dept Biochem & Mol Biol, Syracuse, NY USA

Hanes, Steven D.
论文数: 0 引用数: 0
h-index: 0
机构:
SUNY Upstate Med Univ, Dept Biochem & Mol Biol, Syracuse, NY USA SUNY Upstate Med Univ, Dept Biochem & Mol Biol, Syracuse, NY USA
[38]
Regulation of mRNA cap methylation
[J].
Cowling, Victoria H.
.
BIOCHEMICAL JOURNAL,
2010, 425
:295-302

Cowling, Victoria H.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Dundee, Coll Life Sci, Div Cell Biol & Immunol, Dundee DD1 5EH, Scotland Univ Dundee, Coll Life Sci, Div Cell Biol & Immunol, Dundee DD1 5EH, Scotland
[39]
2′-O methylation of the viral mRNA cap evades host restriction by IFIT family members
[J].
Daffis, Stephane
;
Szretter, Kristy J.
;
Schriewer, Jill
;
Li, Jianqing
;
Youn, Soonjeon
;
Errett, John
;
Lin, Tsai-Yu
;
Schneller, Stewart
;
Zust, Roland
;
Dong, Hongping
;
Thiel, Volker
;
Sen, Ganes C.
;
Fensterl, Volker
;
Klimstra, William B.
;
Pierson, Theodore C.
;
Buller, R. Mark
;
Gale, Michael, Jr.
;
Shi, Pei-Yong
;
Diamond, Michael S.
.
NATURE,
2010, 468 (7322)
:452-456

Daffis, Stephane
论文数: 0 引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA

Szretter, Kristy J.
论文数: 0 引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA

Schriewer, Jill
论文数: 0 引用数: 0
h-index: 0
机构:
St Louis Univ, Sch Med, Dept Mol Microbiol & Immunol, St Louis, MO 63104 USA Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA

Li, Jianqing
论文数: 0 引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA

Youn, Soonjeon
论文数: 0 引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA

Errett, John
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Washington, Sch Med, Dept Immunol, Seattle, WA 98195 USA Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA

Lin, Tsai-Yu
论文数: 0 引用数: 0
h-index: 0
机构:
NIH, Viral Pathogenesis Sect, Viral Dis Lab, Bethesda, MD 20892 USA Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA

Schneller, Stewart
论文数: 0 引用数: 0
h-index: 0
机构:
Auburn Univ, Dept Chem & Biochem, Auburn, AL 36849 USA Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA

Zust, Roland
论文数: 0 引用数: 0
h-index: 0
机构:
Kantonal Hosp St Gallen, Inst Immunobiol, CH-9007 St Gallen, Switzerland Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA

Dong, Hongping
论文数: 0 引用数: 0
h-index: 0
机构:
New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12208 USA Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA

Thiel, Volker
论文数: 0 引用数: 0
h-index: 0
机构:
Kantonal Hosp St Gallen, Inst Immunobiol, CH-9007 St Gallen, Switzerland
Univ Zurich, Vetsuisse Fac, CH-8006 Zurich, Switzerland Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA

Sen, Ganes C.
论文数: 0 引用数: 0
h-index: 0
机构:
Cleveland Clin, Lerner Res Inst, Cleveland, OH 44195 USA Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA

Fensterl, Volker
论文数: 0 引用数: 0
h-index: 0
机构:
Cleveland Clin, Lerner Res Inst, Cleveland, OH 44195 USA Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA

Klimstra, William B.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA 15261 USA Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA

Pierson, Theodore C.
论文数: 0 引用数: 0
h-index: 0
机构:
NIH, Viral Pathogenesis Sect, Viral Dis Lab, Bethesda, MD 20892 USA Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA

Buller, R. Mark
论文数: 0 引用数: 0
h-index: 0
机构:
Midw Reg Ctr Biodef & Emerging Infect Dis Res, St Louis, MO 63104 USA
St Louis Univ, Sch Med, Dept Mol Microbiol & Immunol, St Louis, MO 63104 USA
Pacific NW Reg Ctr Biodef & Emerging Infect Dis R, St Louis, MO 63104 USA
NE Reg Ctr Biodef & Emerging Infect Dis Res, St Louis, MO 63104 USA Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA

Gale, Michael, Jr.
论文数: 0 引用数: 0
h-index: 0
机构:
Midw Reg Ctr Biodef & Emerging Infect Dis Res, St Louis, MO 63104 USA
Univ Washington, Sch Med, Dept Immunol, Seattle, WA 98195 USA
Pacific NW Reg Ctr Biodef & Emerging Infect Dis R, St Louis, MO 63104 USA
NE Reg Ctr Biodef & Emerging Infect Dis Res, St Louis, MO 63104 USA Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA

Shi, Pei-Yong
论文数: 0 引用数: 0
h-index: 0
机构:
Midw Reg Ctr Biodef & Emerging Infect Dis Res, St Louis, MO 63104 USA
New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12208 USA
Pacific NW Reg Ctr Biodef & Emerging Infect Dis R, St Louis, MO 63104 USA
NE Reg Ctr Biodef & Emerging Infect Dis Res, St Louis, MO 63104 USA Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA

Diamond, Michael S.
论文数: 0 引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA
Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA
Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA
Midw Reg Ctr Biodef & Emerging Infect Dis Res, St Louis, MO 63104 USA
Pacific NW Reg Ctr Biodef & Emerging Infect Dis R, St Louis, MO 63104 USA
NE Reg Ctr Biodef & Emerging Infect Dis Res, St Louis, MO 63104 USA Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA
[40]
Assembly and transport of a premessenger RNP particle
[J].
Daneholt, B
.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,
2001, 98 (13)
:7012-7017

Daneholt, B
论文数: 0 引用数: 0
h-index: 0
机构:
Karolinska Inst, Med Nobel Inst, Dept Cell & Mol Biol, SE-17177 Stockholm, Sweden Karolinska Inst, Med Nobel Inst, Dept Cell & Mol Biol, SE-17177 Stockholm, Sweden