全文获取类型
收费全文 | 331篇 |
免费 | 32篇 |
专业分类
363篇 |
出版年
2022年 | 9篇 |
2021年 | 10篇 |
2020年 | 3篇 |
2019年 | 6篇 |
2018年 | 9篇 |
2017年 | 6篇 |
2016年 | 12篇 |
2015年 | 17篇 |
2014年 | 23篇 |
2013年 | 17篇 |
2012年 | 25篇 |
2011年 | 36篇 |
2010年 | 15篇 |
2009年 | 13篇 |
2008年 | 23篇 |
2007年 | 22篇 |
2006年 | 23篇 |
2005年 | 18篇 |
2004年 | 18篇 |
2003年 | 14篇 |
2002年 | 7篇 |
2001年 | 1篇 |
1999年 | 3篇 |
1998年 | 2篇 |
1996年 | 1篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1990年 | 1篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1984年 | 3篇 |
1983年 | 1篇 |
1981年 | 1篇 |
1978年 | 1篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1972年 | 2篇 |
1970年 | 1篇 |
1967年 | 1篇 |
1966年 | 1篇 |
1963年 | 1篇 |
1960年 | 1篇 |
1950年 | 1篇 |
排序方式: 共有363条查询结果,搜索用时 15 毫秒
31.
Insights into the potential function and membrane organization of the TP0435 (Tp17) lipoprotein from Treponema pallidum derived from structural and biophysical analyses 下载免费PDF全文
Chad A. Brautigam Ranjit K. Deka Wei Z. Liu Michael V. Norgard 《Protein science : a publication of the Protein Society》2015,24(1):11-19
The sexually transmitted disease syphilis is caused by the bacterial spirochete Treponema pallidum. This microorganism is genetically intractable, accounting for the large number of putative and undercharacterized members of the pathogen's proteome. In an effort to ascribe a function(s) to the TP0435 (Tp17) lipoprotein, we engineered a soluble variant of the protein (rTP0435) and determined its crystal structure at a resolution of 2.42 Å. The structure is characterized by an eight‐stranded β‐barrel protein with a shallow “basin” at one end of the barrel and an α‐helix stacked on the opposite end. Furthermore, there is a disulfide‐linked dimer of the protein in the asymmetric unit of the crystals. Solution hydrodynamic experiments established that purified rTP0435 is monomeric, but specifically forms the disulfide‐stabilized dimer observed in the crystal structure. The data herein, when considered with previous work on TP0435, imply plausible roles for the protein in either ligand binding, treponemal membrane architecture, and/or pathogenesis. 相似文献
32.
Microautophagy of cytosolic proteins by late endosomes 总被引:2,自引:0,他引:2
Sahu R Kaushik S Clement CC Cannizzo ES Scharf B Follenzi A Potolicchio I Nieves E Cuervo AM Santambrogio L 《Developmental cell》2011,20(1):131-139
Highlights? Late endosomes take up cytosolic proteins through membrane invaginations ? Endosomal microautophagy (eMI) requires multivesicular body formation ? hsc70 mediates selective targeting of cytosolic proteins during eMI ? hsc70 binds to the endosomal membrane through its polybasic cluster 相似文献
33.
34.
35.
36.
The advent of structural genomics has led to a dramatic increase in the number of structures deposited in the Protein Data Bank. The number of new folds, however, still remains a very small fraction of the total number of deposited structures. Recent data on the progress of the structural genomics initiative reveals that more than 85% of target proteins that progress to the stage of data collection and structure determination have a known fold. Enzymes, which tend to exploit reaction space while adopting a common stable scaffold, contribute significantly to this observation. Herein, we evaluate a method to examine the "old fold in a new dataset" scenario likely to be encountered in the structural genomics pipeline. We demonstrate that a fold detection strategy based on secondary structure signatures followed by molecular replacement using a minimalist model can be effectively used to solve the phase problem in X-ray crystallography without further recourse to heavy atom derivatives or multiple anomalous dispersion techniques. Three common folds-the triosephosphate isomerase (TIM), adenine nucleotide alpha hydrolase-like (HUP), and RNA recognition motif (RRM)-were examined using this approach. The results presented herein also provide an estimate of the extent of phase information that can be derived from a single domain in a large multidomain structure. 相似文献
37.
38.
Hepatitis C Virus Infection Modulates Expression of Interferon Stimulatory Gene IFITM1 by Upregulating miR-130A 总被引:1,自引:0,他引:1
J Bhanja Chowdhury S Shrivastava R Steele AM Di Bisceglie R Ray RB Ray 《Journal of virology》2012,86(18):10221-10225
We have examined the underlying mechanism of hepatitis C virus (HCV)-mediated IFITM1 regulation. IFITM1 is a potential target of miR-130a. Our results demonstrated that miR-130a expression was significantly higher in HCV-infected hepatocytes and liver biopsy specimens than in controls. Introduction of anti-miR-130a in hepatocytes increased IFITM1 expression. Hepatocytes stably expressing IFITM1 reduced HCV replication. Together, these results suggested that HCV infection of hepatocytes upregulates miR-130a and that use of anti-miR-130a may have potential for restriction of HCV replication. 相似文献
39.
40.
Chad A. Brautigam Ranjit K. Deka Zhiming Ouyang Mischa Machius Gregory Knutsen Diana R. Tomchick Michael V. Norgard 《Journal of bacteriology》2012,194(24):6771-6781
Metal ion homeostasis is a critical function of many integral and peripheral membrane proteins. The genome of the etiologic agent of syphilis, Treponema pallidum, is compact and devoid of many metabolic enzyme genes. Nevertheless, it harbors genes coding for homologs of several enzymes that typically require either iron or zinc. The product of the tp0971 gene of T. pallidum, designated Tp34, is a periplasmic lipoprotein that is thought to be tethered to the inner membrane of this organism. Previous work on a water-soluble (nonacylated) recombinant version of Tp34 established that this protein binds to Zn2+, which, like other transition metal ions, stabilizes the dimeric form of the protein. In this study, we employed analytical ultracentrifugation to establish that four transition metal ions (Ni2+, Co2+, Cu2+, and Zn2+) readily induce the dimerization of Tp34; Cu2+ (50% effective concentration [EC50] = 1.7 μM) and Zn2+ (EC50 = 6.2 μM) were the most efficacious of these ions. Mutations of the crystallographically identified metal-binding residues hindered the ability of Tp34 to dimerize. X-ray crystallography performed on crystals of Tp34 that had been incubated with metal ions indicated that the binding site could accommodate the metals examined. The findings presented herein, coupled with bioinformatic analyses of related proteins, point to Tp34''s likely role in metal ion homeostasis in T. pallidum. 相似文献