全文获取类型
收费全文 | 398篇 |
免费 | 80篇 |
出版年
2021年 | 4篇 |
2019年 | 4篇 |
2015年 | 10篇 |
2014年 | 9篇 |
2013年 | 9篇 |
2012年 | 21篇 |
2011年 | 16篇 |
2010年 | 18篇 |
2009年 | 12篇 |
2008年 | 14篇 |
2007年 | 14篇 |
2006年 | 17篇 |
2005年 | 16篇 |
2004年 | 15篇 |
2003年 | 18篇 |
2002年 | 22篇 |
2001年 | 22篇 |
2000年 | 8篇 |
1999年 | 7篇 |
1998年 | 5篇 |
1997年 | 4篇 |
1996年 | 5篇 |
1995年 | 5篇 |
1994年 | 4篇 |
1993年 | 4篇 |
1992年 | 9篇 |
1991年 | 14篇 |
1990年 | 14篇 |
1989年 | 6篇 |
1988年 | 9篇 |
1987年 | 12篇 |
1986年 | 8篇 |
1985年 | 13篇 |
1984年 | 15篇 |
1983年 | 10篇 |
1982年 | 9篇 |
1980年 | 4篇 |
1979年 | 7篇 |
1978年 | 6篇 |
1976年 | 6篇 |
1975年 | 6篇 |
1973年 | 3篇 |
1972年 | 5篇 |
1971年 | 3篇 |
1970年 | 3篇 |
1968年 | 5篇 |
1967年 | 4篇 |
1966年 | 3篇 |
1965年 | 3篇 |
1964年 | 3篇 |
排序方式: 共有478条查询结果,搜索用时 125 毫秒
71.
RLIP76 (RalBP1) is an R-Ras effector that mediates adhesion-dependent Rac activation and cell migration
下载免费PDF全文
![点击此处可从《The Journal of cell biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Goldfinger LE Ptak C Jeffery ED Shabanowitz J Hunt DF Ginsberg MH 《The Journal of cell biology》2006,174(6):877-888
The Ras family of small GTPases regulates cell proliferation, spreading, migration and apoptosis, and malignant transformation by binding to several protein effectors. One such GTPase, R-Ras, plays distinct roles in each of these processes, but to date, identified R-Ras effectors were shared with other Ras family members (e.g., H-Ras). We utilized a new database of Ras-interacting proteins to identify RLIP76 (RalBP1) as a novel R-Ras effector. RLIP76 binds directly to R-Ras in a GTP-dependent manner, but does not physically associate with the closely related paralogues H-Ras and Rap1A. RLIP76 is required for adhesion-induced Rac activation and the resulting cell spreading and migration, as well as for the ability of R-Ras to enhance these functions. RLIP76 regulates Rac activity through the adhesion-induced activation of Arf6 GTPase and activation of Arf6 bypasses the requirement for RLIP76 in Rac activation and cell spreading. Thus, we identify a novel R-Ras effector, RLIP76, which links R-Ras to adhesion-induced Rac activation through a GTPase cascade that mediates cell spreading and migration. 相似文献
72.
Christopher J. Raithel Howard S. Ginsberg Ming Lee Prospero 《Journal of Insect Conservation》2006,10(4):317-322
The endangered American burying beetle, Nicrophorus americanus, was monitored on Block Island, RI, USA, from 1991–2003 using mark-recapture population estimates of adults collected in pitfall traps. Populations increased through time, especially after 1994 when a program was initiated that provided carrion for beetle production. Beetle captures increased with increasing temperature and dew point, and decreased with increasing wind speed. Short distance movement was not related to wind direction, while longer distance flights tended to be downwind. Although many individuals flew considerable distances along transects, most recaptures were in traps near the point of release. These behaviors probably have counterbalancing effects on population estimates.The U.S. Goverment's right to retain a non-exclusive, royalty-free license in and to any copyright is acknowledged. 相似文献
73.
Wall teichoic acids (WTAs) are anionic polymers that coat the cell walls of Gram-positive bacteria. Because they are essential for survival or virulence in many organisms, the enzymes involved in the biosynthesis of WTAs are attractive antibiotic targets. The first committed step in the WTA biosynthetic pathway in Bacillus subtilis is catalyzed by TagA, which transfers N-acetylmannosamine (ManNAc) to the C4 hydroxyl of a membrane-anchored N-acetylglucosaminyl diphospholipid (GlcNAc-pp-undecaprenyl, lipid I) to make ManNAc-beta-(1,4)-GlcNAc-pp-undecaprenyl (lipid II). We have previously shown that TagA utilizes an alternative substrate containing a saturated C(13)H(27) lipid chain. Here we use unnatural substrates and products to establish the lipid preferences of the enzyme and to characterize the kinetic mechanism. We report that TagA is a metal ion-independent glycosyltransferase that follows a steady-state ordered Bi-Bi mechanism in which UDP-ManNAc binds first and UDP is released last. TagA shares homology with a large family of bacterial glycosyltransferases, and the work described here should facilitate structural analysis of the enzyme in complex with its substrates. 相似文献
74.
In this study, a cleavable signal peptide fused to the enhanced green fluorescent protein (EGFP) was tagged to the extracellular
N-terminus of the human dopamine D2 receptor short and long isoforms (D2S and D2L). Ligand-binding properties of EGFP-tagged
receptors were essentially unchanged in comparison to their respective wild-type receptors. The dopamine-mediated activation
of both EGFP-D2 isoforms generated a robust inhibition of adenylyl cyclase type 5 in intact cells. In addition, the receptor
density of EGFP-D2S and EGFP-D2L in transfected human embryonic kidney 293 (HEK293) cells was not altered when compared to
cells transfected with the untagged D2S and D2L. However, the receptor densities of untagged and EGFP-tagged D2L were significantly
lower in comparison to those measured with D2S constructs. Moreover, the receptor density of EGFP-D2S and EGFP-D2L was differentially
upregulated in cells treated with antipsychotic drugs. As assessed by confocal microscopy, both EGFP-D2 isoforms were present
on the cell surface. Notably, in contrast to the predominant plasma membrane localization of EGFP-D2S, EGFP-D2L was visualized
both on the plasma membrane and intracellularly before dopamine exposure. Importantly, EGFP-D2S and EGFP-D2L are robustly
internalized after dopamine treatment. Overall, our data suggest a differential intracellular sorting of D2S and D2L. 相似文献
75.
76.
The products of genes that cause cerebral cavernous malformations (CCM1/KRIT1, CCM2, and CCM3) physically interact. CCM1/KRIT1 links this complex to endothelial cell (EC) junctions and maintains junctional integrity in part by inhibiting RhoA. Heart of glass (HEG1), a transmembrane protein, associates with KRIT1. In this paper, we show that the KRIT1 band 4.1, ezrin, radixin, and moesin (FERM) domain bound the HEG1 C terminus (Kd = 1.2 µM) and solved the structure of this assembly. The KRIT1 F1 and F3 subdomain interface formed a hydrophobic groove that binds HEG1(Tyr1,380-Phe1,381), thus defining a new mode of FERM domain–membrane protein interaction. This structure enabled design of KRIT1(L717,721A), which exhibited a >100-fold reduction in HEG1 affinity. Although well folded and expressed, KRIT1(L717,721A) failed to target to EC junctions or complement the effects of KRIT1 depletion on zebrafish cardiovascular development or Rho kinase activation in EC. These data establish that this novel FERM–membrane protein interaction anchors CCM1/KRIT1 at EC junctions to support cardiovascular development. 相似文献
77.
Gene P. Ables Kryscilla Jian Zhang Yang Silke Vogel Antonio Hernandez-Ono Shuiqing Yu Jason J. Yuen Susan Birtles Linda K. Buckett Andrew V. Turnbull Ira J. Goldberg William S. Blaner Li-Shin Huang Henry N. Ginsberg 《Journal of lipid research》2012,53(11):2364-2379
Acyl CoA:diacylglycerol acyltransferase (DGAT) 1 catalyzes the final step of
triglyceride (TG) synthesis. We show that acute administration of a DGAT1 inhibitor
(DGAT1i) by oral gavage or genetic deletion of intestinal Dgat1
(intestine-Dgat1−/−)
markedly reduced postprandial plasma TG and retinyl ester excursions by inhibiting
chylomicron secretion in mice. Loss of DGAT1 activity did not affect the efficiency
of retinol esterification, but it did reduce TG and retinoid accumulation in the
small intestine. In contrast, inhibition of microsomal triglyceride transfer protein
(MTP) reduced chylomicron secretion after oral fat/retinol loads, but with
accumulation of dietary TG and retinoids in the small intestine. Lack of intestinal
accumulation of TG and retinoids in DGAT1i-treated or
intestine-Dgat1−/− mice
resulted, in part, from delayed gastric emptying associated with increased plasma
levels of glucagon-like peptide (GLP)-1. However, neither bypassing the stomach
through duodenal oil injection nor inhibiting the receptor for GLP-1 normalized
postprandial TG or retinyl esters excursions in the absence of DGAT1 activity. In
summary, intestinal DGAT1 inhibition or deficiency acutely delayed gastric emptying
and inhibited chylomicron secretion; however, the latter occurred when gastric
emptying was normal or when lipid was administered directly into the small intestine.
Long-term hepatic retinoid metabolism was not impacted by DGAT1 inhibition. 相似文献
78.
79.
Marsden CD Woodroffe R Mills MG McNutt JW Creel S Groom R Emmanuel M Cleaveland S Kat P Rasmussen GS Ginsberg J Lines R André JM Begg C Wayne RK Mable BK 《Molecular ecology》2012,21(6):1379-1393
Deciphering patterns of genetic variation within a species is essential for understanding population structure, local adaptation and differences in diversity between populations. Whilst neutrally evolving genetic markers can be used to elucidate demographic processes and genetic structure, they are not subject to selection and therefore are not informative about patterns of adaptive variation. As such, assessments of pertinent adaptive loci, such as the immunity genes of the major histocompatibility complex (MHC), are increasingly being incorporated into genetic studies. In this study, we combined neutral (microsatellite, mtDNA) and adaptive (MHC class II DLA‐DRB1 locus) markers to elucidate the factors influencing patterns of genetic variation in the African wild dog (Lycaon pictus); an endangered canid that has suffered extensive declines in distribution and abundance. Our genetic analyses found all extant wild dog populations to be relatively small (Ne < 30). Furthermore, through coalescent modelling, we detected a genetic signature of a recent and substantial demographic decline, which correlates with human expansion, but contrasts with findings in some other African mammals. We found strong structuring of wild dog populations, indicating the negative influence of extensive habitat fragmentation and loss of gene flow between habitat patches. Across populations, we found that the spatial and temporal structure of microsatellite diversity and MHC diversity were correlated and strongly influenced by demographic stability and population size, indicating the effects of genetic drift in these small populations. Despite this correlation, we detected signatures of selection at the MHC, implying that selection has not been completely overwhelmed by genetic drift. 相似文献
80.