全文获取类型
收费全文 | 2756篇 |
免费 | 210篇 |
国内免费 | 1篇 |
专业分类
2967篇 |
出版年
2024年 | 5篇 |
2023年 | 36篇 |
2022年 | 70篇 |
2021年 | 140篇 |
2020年 | 77篇 |
2019年 | 90篇 |
2018年 | 87篇 |
2017年 | 71篇 |
2016年 | 121篇 |
2015年 | 156篇 |
2014年 | 205篇 |
2013年 | 186篇 |
2012年 | 224篇 |
2011年 | 224篇 |
2010年 | 115篇 |
2009年 | 102篇 |
2008年 | 133篇 |
2007年 | 113篇 |
2006年 | 100篇 |
2005年 | 104篇 |
2004年 | 106篇 |
2003年 | 95篇 |
2002年 | 67篇 |
2001年 | 26篇 |
2000年 | 28篇 |
1999年 | 25篇 |
1998年 | 14篇 |
1997年 | 17篇 |
1996年 | 15篇 |
1995年 | 7篇 |
1994年 | 10篇 |
1992年 | 15篇 |
1991年 | 8篇 |
1990年 | 11篇 |
1989年 | 8篇 |
1988年 | 13篇 |
1987年 | 16篇 |
1986年 | 7篇 |
1985年 | 11篇 |
1984年 | 14篇 |
1983年 | 5篇 |
1981年 | 7篇 |
1979年 | 9篇 |
1977年 | 9篇 |
1976年 | 9篇 |
1975年 | 9篇 |
1972年 | 5篇 |
1971年 | 5篇 |
1966年 | 4篇 |
1965年 | 5篇 |
排序方式: 共有2967条查询结果,搜索用时 15 毫秒
991.
Although mutations in cardiac myosin binding protein-C (cMyBP-C) cause heart disease, its role in muscle contraction is not well understood. A mechanism remains elusive partly because the protein can have multiple effects, such as dual biphasic activation and inhibition observed in actin motility assays. Here we develop a mathematical model for the interaction of cMyBP-C with the contractile proteins actin and myosin and the regulatory protein tropomyosin. We use this model to show that a drag-activation-competition mechanism accurately describes actin motility measurements, while models lacking either drag or competition do not. These results suggest that complex effects can arise simply from cMyBP-C binding to actin. 相似文献
992.
Elizabeth M. Haynes Sreeja B. Asokan Samantha J. King Heath E. Johnson Jason M. Haugh James E. Bear 《The Journal of cell biology》2015,209(6):803-812
The lamellipodium is an important structure for cell migration containing branched actin nucleated via the Arp2/3 complex. The formation of branched actin is relatively well studied, but less is known about its disassembly and how this influences migration. GMF is implicated in both Arp2/3 debranching and inhibition of Arp2/3 activation. Modulation of GMFβ, a ubiquitous GMF isoform, by depletion or overexpression resulted in changes in lamellipodial dynamics, branched actin content, and migration. Acute pharmacological inhibition of Arp2/3 by CK-666, coupled to quantitative live-cell imaging of the complex, showed that depletion of GMFβ decreased the rate of branched actin disassembly. These data, along with mutagenesis studies, suggest that debranching (not inhibition of Arp2/3 activation) is a primary activity of GMFβ in vivo. Furthermore, depletion or overexpression of GMFβ disrupted the ability of cells to directionally migrate to a gradient of fibronectin (haptotaxis). These data suggest that debranching by GMFβ plays an important role in branched actin regulation, lamellipodial dynamics, and directional migration. 相似文献
993.
994.
995.
Fan Xia Matthew?N. Bainbridge Tiong?Yang Tan Michael?F. Wangler Angela?E. Scheuerle Elaine?H. Zackai Margaret?H. Harr V.?Reid Sutton Roopa?L. Nalam Wenmiao Zhu Margot Nash Monique?M. Ryan Joy Yaplito-Lee Jill?V. Hunter Matthew?A. Deardorff Samantha?J. Penney Arthur?L. Beaudet Sharon?E. Plon Eric?A. Boerwinkle James?R. Lupski Christine?M. Eng Donna?M. Muzny Yaping Yang Richard?A. Gibbs 《American journal of human genetics》2014,94(5):784-789
Clinical whole-exome sequencing (WES) for identification of mutations leading to Mendelian disease has been offered to the medical community since 2011. Clinically undiagnosed neurological disorders are the most frequent basis for test referral, and currently, approximately 25% of such cases are diagnosed at the molecular level. To date, there are approximately 4,000 “known” disease-associated loci, and many are associated with striking dysmorphic features, making genotype-phenotype correlations relatively straightforward. A significant fraction of cases, however, lack characteristic dysmorphism or clinical pathognomonic traits and are dependent upon molecular tests for definitive diagnoses. Further, many molecular diagnoses are guided by recent gene-disease association discoveries. Hence, there is a critical interplay between clinical testing and research leading to gene-disease association discovery. Here, we describe four probands, all of whom presented with hypotonia, intellectual disability, global developmental delay, and mildly dysmorphic facial features. Three of the four also had sleep apnea. Each was a simplex case without a remarkable family history. Using WES, we identified AHDC1 de novo truncating mutations that most likely cause this genetic syndrome. 相似文献
996.
Elisa Venturi Elena Galfré Fiona O’Brien Samantha?J. Pitt Stuart Bellamy Richard?B. Sessions Rebecca Sitsapesan 《Biophysical journal》2014,106(4):824-833
We have previously shown that FKBP12 associates with RyR2 in cardiac muscle and that it modulates RyR2 function differently to FKBP12.6. We now investigate how these proteins affect the single-channel behavior of RyR1 derived from rabbit skeletal muscle. Our results show that FKBP12.6 activates and FKBP12 inhibits RyR1. It is likely that both proteins compete for the same binding sites on RyR1 because channels that are preactivated by FKBP12.6 cannot be subsequently inhibited by FKBP12. We produced a mutant FKBP12 molecule (FKBP12E31Q/D32N/W59F) where the residues Glu31, Asp32, and Trp59 were converted to the corresponding residues in FKBP12.6. With respect to the functional regulation of RyR1 and RyR2, the FKBP12E31Q/D32N/W59F mutant lost all ability to behave like FKBP12 and instead behaved like FKBP12.6. FKBP12E31Q/D32N/W59F activated RyR1 but was not capable of activating RyR2. In conclusion, FKBP12.6 activates RyR1, whereas FKBP12 activates RyR2 and this selective activator phenotype is determined within the amino acid residues Glu31, Asp32, and Trp59 in FKBP12 and Gln31, Asn32, and Phe59 in FKBP12.6. The opposing but different effects of FKBP12 and FKBP12.6 on RyR1 and RyR2 channel gating provide scope for diversity of regulation in different tissues. 相似文献
997.
998.
999.
1000.
Amin Afrazi Maria F. Branca Chhinder P. Sodhi Misty Good Yukihiro Yamaguchi Charlotte E. Egan Peng Lu Hongpeng Jia Shahab Shaffiey Joyce Lin Congrong Ma Garrett Vincent Thomas Prindle Jr. Samantha Weyandt Matthew D. Neal John A. Ozolek John Wiersch Markus Tschurtschenthaler Chiyo Shiota George K. Gittes Timothy R. Billiar Kevin Mollen Arthur Kaser Richard Blumberg David J. Hackam 《The Journal of biological chemistry》2014,289(14):9584-9599