全文获取类型
收费全文 | 378篇 |
免费 | 48篇 |
国内免费 | 1篇 |
出版年
2021年 | 5篇 |
2019年 | 3篇 |
2017年 | 3篇 |
2016年 | 11篇 |
2015年 | 16篇 |
2014年 | 12篇 |
2013年 | 17篇 |
2012年 | 29篇 |
2011年 | 24篇 |
2010年 | 14篇 |
2009年 | 13篇 |
2008年 | 23篇 |
2007年 | 25篇 |
2006年 | 23篇 |
2005年 | 27篇 |
2004年 | 20篇 |
2003年 | 19篇 |
2002年 | 12篇 |
2001年 | 17篇 |
2000年 | 13篇 |
1999年 | 16篇 |
1997年 | 4篇 |
1996年 | 4篇 |
1995年 | 5篇 |
1994年 | 4篇 |
1993年 | 4篇 |
1992年 | 3篇 |
1991年 | 2篇 |
1990年 | 4篇 |
1989年 | 4篇 |
1988年 | 5篇 |
1987年 | 4篇 |
1986年 | 3篇 |
1984年 | 3篇 |
1982年 | 3篇 |
1981年 | 6篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1978年 | 3篇 |
1976年 | 2篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1971年 | 2篇 |
1970年 | 1篇 |
1969年 | 3篇 |
1968年 | 3篇 |
1967年 | 1篇 |
1931年 | 1篇 |
1902年 | 1篇 |
1899年 | 1篇 |
排序方式: 共有427条查询结果,搜索用时 15 毫秒
61.
62.
63.
Hydration of protein cavities influences protein stability, dynamics, and function. Protein active sites usually contain water molecules that, upon ligand binding, are either displaced into bulk solvent or retained to mediate protein–ligand interactions. The contribution of water molecules to ligand binding must be accounted for to compute accurate values of binding affinities. This requires estimation of the extent of hydration of the binding site. However, it is often difficult to identify the water molecules involved in the binding process when ligands bind on the surface of a protein. Cytochrome P450cam is, therefore, an ideal model system because its substrate binds in a buried active site, displacing partially disordered solvent, and the protein is well characterized experimentally. We calculated the free energy differences for having five to eight water molecules in the active site cavity of the unliganded enzyme from molecular dynamics simulations by thermodynamic integration employing a three-stage perturbation scheme. The computed free energy differences between the hydration states are small (within 12 kJ mol−1) but distinct. Consistent with the crystallographic determination and studies employing hydrostatic pressure, we calculated that, although ten water molecules could in principle occupy the volume of the active site, occupation by five to six water molecules is thermodynamically most favorable. Proteins 32:381–396, 1998. © 1998 Wiley-Liss, Inc. 相似文献
64.
Background
The p49/STRAP (or SRFBP1) protein was recently identified in our laboratory as a cofactor of serum response factor that contributes to the regulation of SRF target genes in the heart. 相似文献65.
Ying Liu Cynthia Helms Wilson Liao Lisa C. Zaba Shenghui Duan Jennifer Gardner Carol Wise Andrew Miner M. J. Malloy Clive R. Pullinger John P. Kane Scott Saccone Jane Worthington Ian Bruce Pui–Yan Kwok Alan Menter James Krueger Anne Barton Nancy L. Saccone Anne M. Bowcock 《PLoS genetics》2008,4(4)
A genome-wide association study was performed to identify genetic factors involved in susceptibility to psoriasis (PS) and psoriatic arthritis (PSA), inflammatory diseases of the skin and joints in humans. 223 PS cases (including 91 with PSA) were genotyped with 311,398 single nucleotide polymorphisms (SNPs), and results were compared with those from 519 Northern European controls. Replications were performed with an independent cohort of 577 PS cases and 737 controls from the U.S., and 576 PSA patients and 480 controls from the U.K.. Strongest associations were with the class I region of the major histocompatibility complex (MHC). The most highly associated SNP was rs10484554, which lies 34.7 kb upstream from HLA-C (P = 7.8×10−11, GWA scan; P = 1.8×10−30, replication; P = 1.8×10−39, combined; U.K. PSA: P = 6.9×10−11). However, rs2395029 encoding the G2V polymorphism within the class I gene HCP5 (combined P = 2.13×10−26 in U.S. cases) yielded the highest ORs with both PS and PSA (4.1 and 3.2 respectively). This variant is associated with low viral set point following HIV infection and its effect is independent of rs10484554. We replicated the previously reported association with interleukin 23 receptor and interleukin 12B (IL12B) polymorphisms in PS and PSA cohorts (IL23R: rs11209026, U.S. PS, P = 1.4×10−4; U.K. PSA: P = 8.0×10−4; IL12B:rs6887695, U.S. PS, P = 5×10−5 and U.K. PSA, P = 1.3×10−3) and detected an independent association in the IL23R region with a SNP 4 kb upstream from IL12RB2 (P = 0.001). Novel associations replicated in the U.S. PS cohort included the region harboring lipoma HMGIC fusion partner (LHFP) and conserved oligomeric golgi complex component 6 (COG6) genes on chromosome 13q13 (combined P = 2×10−6 for rs7993214; OR = 0.71), the late cornified envelope gene cluster (LCE) from the Epidermal Differentiation Complex (PSORS4) (combined P = 6.2×10−5 for rs6701216; OR 1.45) and a region of LD at 15q21 (combined P = 2.9×10−5 for rs3803369; OR = 1.43). This region is of interest because it harbors ubiquitin-specific protease-8 whose processed pseudogene lies upstream from HLA-C. This region of 15q21 also harbors the gene for SPPL2A (signal peptide peptidase like 2a) which activates tumor necrosis factor alpha by cleavage, triggering the expression of IL12 in human dendritic cells. We also identified a novel PSA (and potentially PS) locus on chromosome 4q27. This region harbors the interleukin 2 (IL2) and interleukin 21 (IL21) genes and was recently shown to be associated with four autoimmune diseases (Celiac disease, Type 1 diabetes, Grave''s disease and Rheumatoid Arthritis). 相似文献
66.
67.
68.
69.
Frances MK Williams 《Arthritis research & therapy》2009,11(5):130-2
The field of biomarkers is a growing one, particularly in osteoarthritis (OA). OA is the most common disabling condition in
older persons and a major cause of morbidity. While the debate continues about which of the involved tissues - cartilage,
bone or synovium - is the most important in OA aetiology, there is no doubt that the three develop abnormalities in concert;
perhaps a truly useful biomarker will reflect just that. While efforts continue to identify reliable biomarkers useful for
characterising the status, prognosis and measurement of treatment response in OA, combining existing biomarkers to improve
their accuracy looks promising. 相似文献
70.
Gabriele Helms Bernd-Arno Behrens Martin Stolorz Patrick Wefstaedt Ingo Nolte 《Biomedical engineering online》2009,8(1):36-9