全文获取类型
收费全文 | 236篇 |
免费 | 27篇 |
出版年
2023年 | 1篇 |
2021年 | 7篇 |
2020年 | 2篇 |
2019年 | 3篇 |
2018年 | 2篇 |
2017年 | 3篇 |
2016年 | 9篇 |
2015年 | 10篇 |
2014年 | 15篇 |
2013年 | 20篇 |
2012年 | 27篇 |
2011年 | 13篇 |
2010年 | 17篇 |
2009年 | 11篇 |
2008年 | 7篇 |
2007年 | 9篇 |
2006年 | 12篇 |
2005年 | 9篇 |
2004年 | 4篇 |
2003年 | 7篇 |
2002年 | 4篇 |
2001年 | 7篇 |
2000年 | 7篇 |
1999年 | 6篇 |
1998年 | 4篇 |
1997年 | 1篇 |
1996年 | 3篇 |
1995年 | 4篇 |
1994年 | 1篇 |
1992年 | 5篇 |
1991年 | 4篇 |
1990年 | 5篇 |
1989年 | 2篇 |
1988年 | 3篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 3篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 3篇 |
1971年 | 1篇 |
1970年 | 1篇 |
排序方式: 共有263条查询结果,搜索用时 15 毫秒
111.
112.
Manoj Kumar Tripathy Zulfazal Ahmed Jayashree Sashikant Ladha Debashis Mitra 《Apoptosis : an international journal on programmed cell death》2010,15(12):1453-1460
One of the hallmarks of Human Immunodeficiency Virus-1 (HIV-1) infection is progressive depletion of the infected and bystander
CD4+ T-cells by apoptosis. Different mitochondrial proteins have been implicated in this apoptotic process; however, the role
of different subunits of mitochondrial oxidative phosphorylation (OXPHOS) complexes in apoptosis is not clearly understood.
Some of the OXPHOS complex subunits seem to perform other functions in addition to their primary role in energy generating
process. GRIM-19 (gene associated with retinoid-interferon-induced-mortality-19), a subunit of mitochondrial complex-I was
previously implicated in Interferon-β and retionoic acid induced apoptosis in many tumor cells. In this study we report, using
differential gene expression analysis, that GRIM-19 is up-regulated in HIV-1 infected apoptotic T-cells. A temporal up regulation
of this subunit was observed in different HIV-1 infected T-cell lines and human PBMC and the extent of increase correlated
to increasing apoptosis and virus production. Moreover, silencing GRIM-19 in HIV-1 infected cells reduced apoptosis, indicating
its involvement in HIV-1 induced T-cell death. 相似文献
113.
114.
115.
Elevated hepatic fatty acid elongase-5 activity affects multiple pathways controlling hepatic lipid and carbohydrate composition 总被引:4,自引:0,他引:4
Wang Y Torres-Gonzalez M Tripathy S Botolin D Christian B Jump DB 《Journal of lipid research》2008,49(7):1538-1552
Hepatic fatty acid elongase-5 (Elovl-5) plays an important role in long chain monounsaturated and polyunsaturated fatty acid synthesis. Elovl-5 activity is regulated during development, by diet, hormones, and drugs, and in chronic disease. This report examines the impact of elevated Elovl-5 activity on hepatic function. Adenovirus-mediated induction of Elovl5 activity in livers of C57BL/6 mice increased hepatic and plasma levels of dihomo-gamma-linolenic acid (20:3,n-6) while suppressing hepatic arachidonic acid (20:4,n-6) and docosahexaenoic acid (22:6,n-3) content. The fasting-refeeding response of peroxisome proliferator-activated receptor alpha-regulated genes was attenuated in mice with elevated Elovl5 activity. In contrast, the fasting-refeeding response of hepatic sterol-regulatory element binding protein-1 (SREBP-1)-regulated and carbohydrate-regulatory element binding protein/Max-like factor X-regulated genes, Akt and glycogen synthase kinase (Gsk)-3beta phosphorylation, and the accumulation of hepatic glycogen content and nuclear SREBP-1 were not impaired by elevated Elovl5 activity. Hepatic triglyceride content and the phosphorylation of AMP-activated kinase alpha and Jun kinase 1/2 were reduced by elevated Elovl5 activity. Hepatic phosphoenolpyruvate carboxykinase expression was suppressed, while hepatic glycogen content and phosphorylated Gsk-3beta were significantly increased, in livers of fasted mice with increased Elovl5 activity. As such, hepatic Elovl5 activity may affect hepatic glucose production during fasting. In summary, Elovl5-induced changes in hepatic fatty acid content affect multiple pathways regulating hepatic lipid and carbohydrate composition. 相似文献
116.
The skeletal muscle (RyR1) and cardiac muscle (RyR2) ryanodine receptor calcium release channels contain a single, conserved calmodulin (CaM) binding domain, yet are differentially regulated by CaM. Here, we report that high-affinity [(35)S]CaM binding to RyR1 is driven by favorable enthalpic and entropic contributions at Ca(2+) concentrations from <0.01 to 100 microM. At 0.15 microM Ca(2+), [(35)S]CaM bound to RyR2 with decreased affinity and binding enthalpy compared with RyR1. The rates of [(35)S]CaM dissociation from RyR1 increased as the temperature was raised, whereas at 0.15 microM Ca(2+) the rate from RyR2 was little affected. The results suggest major differences in the energetics of CaM binding to and dissociation from RyR1 and RyR2. 相似文献
117.
Babu J.N. Reddy Suvranta Tripathy Michael Vershinin Marvin E. Tanenbaum Jing Xu Michelle Mattson‐Hoss Karim Arabi Dail Chapman Tory Doolin Changbong Hyeon Steven P. Gross 《Traffic (Copenhagen, Denmark)》2017,18(10):658-671
The kinesin family proteins are often studied as prototypical molecular motors; a deeper understanding of them can illuminate regulation of intracellular transport. It is typically assumed that they function identically. Here we find that this assumption of homogeneous function appears incorrect: variation among motors’ velocities in vivo and in vitro is larger than the stochastic variation expected for an ensemble of “identical” motors. When moving on microtubules, slow and fast motors are persistently slow, and fast, respectively. We develop theory that provides quantitative criteria to determine whether the observed single‐molecule variation is too large to be generated from an ensemble of identical molecules. To analyze such heterogeneity, we group traces into homogeneous sub‐ensembles. Motility studies varying the temperature, pH and glycerol concentration suggest at least 2 distinct functional states that are independently affected by external conditions. We end by investigating the functional ramifications of such heterogeneity through Monte‐Carlo multi‐motor simulations. 相似文献
118.
Tripathy R Angeles TS Yang SX Mallamo JP 《Bioorganic & medicinal chemistry letters》2008,18(12):3551-3555
An immobilized Staurosporine aglycone isostere where one of the indole nitrogen atoms was replaced by carbon has been sequentially functionalized to generate compounds inhibiting TrkA kinase. In the first phase, initial screening of a library of C13-hydroxymethyl-7-oxo-indenopyrrolocarbazoles resulted in several potent compounds, one of which was further optimized to generate the corresponding carbamates on solid phase. Some of the major carbamate diastereomers were found to be several-fold more potent than their alcohol parents. Synthesis, SAR analysis, kinase selectivity, and anti-tumor properties of a TrkA inhibitor (12a) are discussed. 相似文献
119.
Dietary resistant starch upregulates total GLP-1 and PYY in a sustained day-long manner through fermentation in rodents 总被引:1,自引:0,他引:1
Zhou J Martin RJ Tulley RT Raggio AM McCutcheon KL Shen L Danna SC Tripathy S Hegsted M Keenan MJ 《American journal of physiology. Endocrinology and metabolism》2008,295(5):E1160-E1166
Glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are anti-diabetes/obesity hormones secreted from the gut after meal ingestion. We have shown that dietary-resistant starch (RS) increased GLP-1 and PYY secretion, but the mechanism remains unknown. RS is a fermentable fiber that lowers the glycemic index of the diet and liberates short-chain fatty acids (SCFAs) through fermentation in the gut. This study investigates the two possible mechanisms by which RS stimulates GLP-1 and PYY secretion: the effect of a meal or glycemic index, and the effect of fermentation. Because GLP-1 and PYY secretions are stimulated by nutrient availability in the gut, the timing of blood sample collections could influence the outcome when two diets with different glycemic indexes are compared. Thus we examined GLP-1 and PYY plasma levels at various time points over a 24-h period in RS-fed rats. In addition, we tested proglucagon (a precursor to GLP-1) and PYY gene expression patterns in specific areas of the gut of RS-fed rats and in an enteroendocrine cell line following exposure to SCFAs in vitro. Our findings are as follows. 1) RS stimulates GLP-1 and PYY secretion in a substantial day-long manner, independent of meal effect or changes in dietary glycemia. 2) Fermentation and the liberation of SCFAs in the lower gut are associated with increased proglucagon and PYY gene expression. 3) Glucose tolerance, an indicator of increased active forms of GLP-1 and PYY, was improved in RS-fed diabetic mice. We conclude that fermentation of RS is most likely the primary mechanism for increased endogenous secretions of total GLP-1 and PYY in rodents. Thus any factor that affects fermentation should be considered when dietary fermentable fiber is used to stimulate GLP-1 and PYY secretion. 相似文献