全文获取类型
收费全文 | 205篇 |
免费 | 7篇 |
国内免费 | 2篇 |
出版年
2023年 | 2篇 |
2022年 | 1篇 |
2021年 | 4篇 |
2020年 | 1篇 |
2019年 | 3篇 |
2018年 | 5篇 |
2016年 | 7篇 |
2015年 | 9篇 |
2014年 | 12篇 |
2013年 | 16篇 |
2012年 | 14篇 |
2011年 | 9篇 |
2010年 | 18篇 |
2009年 | 8篇 |
2008年 | 5篇 |
2007年 | 14篇 |
2006年 | 18篇 |
2005年 | 13篇 |
2004年 | 9篇 |
2003年 | 17篇 |
2002年 | 9篇 |
2001年 | 7篇 |
2000年 | 3篇 |
1999年 | 1篇 |
1995年 | 1篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1978年 | 1篇 |
排序方式: 共有214条查询结果,搜索用时 46 毫秒
51.
Ca2+-dependent inhibition of NHE3 requires PKC alpha which binds to E3KARP to decrease surface NHE3 containing plasma membrane complexes 总被引:1,自引:0,他引:1
Lee-Kwon W Kim JH Choi JW Kawano K Cha B Dartt DA Zoukhri D Donowitz M 《American journal of physiology. Cell physiology》2003,285(6):C1527-C1536
The intestinal brush border (BB) Na+/H+ exchanger isoform 3 (NHE3) is acutely inhibited by elevation in the concentration of free intracellular Ca2+ ([Ca2+]i) by the cholinergic agonist carbachol and Ca2+ ionophores in a protein kinase C (PKC)-dependent manner. We previously showed that elevating [Ca2+]i with ionomycin rapidly inhibited NHE3 activity and decreased the amount of NHE3 on the plasma membrane in a manner that depended on the presence of the PDZ domain-containing protein E3KARP (NHE3 kinase A regulatory protein, also called NHERF2). The current studies were performed in PS120 fibroblasts (NHE-null cell line) stably transfected with NHE3 and E3KARP to probe the mechanism of PKC involvement in Ca2+ regulation of NHE3. Pretreatment with the general PKC inhibitor, GF109203X prevented ionomycin inhibition of NHE3 without altering basal NHE3 activity. Similarly, the Ca2+-mediated inhibition of NHE3 activity was blocked after pretreatment with the conventional PKC inhibitor Gö-6976 and a specific PKC pseudosubstrate-derived inhibitor peptide. [Ca2+]i elevation caused translocation of PKC from cytosol to membrane. PKC bound to the PDZ1 domain of GST-E3KARP in vitro in a Ca2+-dependent manner. PKC and E3KARP coimmunoprecipitated from cell lysates; this occurred to a lesser extent at basal [Ca2+]i and was increased with ionomycin exposure. Biotinylation studies demonstrated that [Ca2+]i elevation induced oligomerization of NHE3 in total lysates and decreased the amount of plasma membrane NHE3. Treatment with PKC inhibitors did not affect the oligomerization of NHE3 but did prevent the decrease in surface amount of NHE3. These results suggest that PKC is not necessary for the Ca2+-dependent formation of the NHE3 plasma membrane complex, although it is necessary for decreasing the membrane amounts of NHE3, probably by stimulating NHE3 endocytosis. Na absorption; PDZ domains; signal complex 相似文献
52.
Turner SC Esbenshade TA Bennani YL Hancock AA 《Bioorganic & medicinal chemistry letters》2003,13(13):2131-2135
The synthesis and biological evaluation of novel cycloheptaquinoline antagonists of the human H(3) receptor are described. Two series of compounds, bearing either an amino substituent or an alkyne linker at the 11-position, were investigated. Modifications of the amino substituents, optimization of chain length and the effect of conformational restraints are described. Several compounds with high affinity and selectivity for the H(3) receptor were discovered. 相似文献
53.
54.
Rochdi MD Watier V La Madeleine C Nakata H Kozasa T Parent JL 《The Journal of biological chemistry》2002,277(43):40751-40759
Although ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) is a PDZ domain-containing protein known to bind to various channels, receptors, cytoskeletal elements, and cytoplasmic proteins, there is still very little evidence for a role of EBP50 in the regulation of receptor signal transduction. In this report, we show that EBP50 inhibits the phospholipase C (PLC)-beta-mediated inositol phosphate production of a Galpha(q)-coupled receptor as well as PLC-beta activation by the constitutively active Galpha(q)-R183C mutant. Coimmunoprecipitation experiments revealed that EBP50 interacts with Galpha(q) and to a greater extent with Galpha(q)-R183C. Agonist stimulation of the thromboxane A(2) receptor (TP receptor) resulted in an increased interaction between EBP50 and Galpha(q), suggesting that EBP50 preferentially interacts with activated Galpha(q). We also demonstrate that EBP50 inhibits Galpha(q) signaling by preventing the interaction between Galpha(q) and the TP receptor and between activated Galpha(q) and PLC-beta1. Investigation of the EBP50 regions involved in Galpha(q) binding indicated that its two PDZ domains are responsible for this interaction. This study constitutes the first demonstration of an interaction between a G protein alpha subunit and another protein through a PDZ domain, with broad implications in the regulation of diverse physiological systems. 相似文献
55.
Yassine El Ghallab Jamal Jamal Eddine Achraf Aainouss My Driss El Messaoudi Mohamed Dakir Sanae Derfoufi 《化学与生物多样性》2023,20(10):e202300895
Syzygium aromaticum is used in traditional and modern medicine for its various and outstanding pharmacological properties. Here, we studied the chemical composition of hexane extract and non-polar fractions (NPF) obtained from the maceration and fractionation of clove buds, in order to evaluate their in vitro antimycobacterial activity, as well as their contribution against efflux pump (EP) resistance through molecular docking experiments. The gas chromatography-mass spectrometry (GC–MS) analysis of the volatile profiles revealed the presence of eugenol, followed by eugenyl acetate, and β-caryophyllene as common major compounds. According to Resazurin microtiter assay (REMA), Mycobacterium tuberculosis H37Rv strain was sensitive to all volatile samples at concentration range between 10 and 100 μg/mL. The NPF of ethanol extract was the best inhibitor with a MIC=10 μg/mL. The in silico study revealed a strong binding affinity between eugenol and Mmr EP protein (−8.1 Kcal/mol), involving two binding modes of hydrogen bond and π-alkyl interactions. The non-polarity character of clove volatile constituents, and their potential additive or synergistic effects could be responsible for the antimycobacterial activity. In addition, these findings suggest the benefic effect of eugenol in the management of mycobacterium drug resistance, whether as potential inhibitor of Mmr drug EP, or modulator during combination therapy. 相似文献
56.
Mohamed Romdhani Ismail Dergaa Imen Moussa-Chamari Nizar Souissi Yassine Chaabouni Kacem Mahdouani Olfa Abene Tarak Driss Karim Chamari Omar Hammouda 《Biology of sport / Institute of Sport》2021,38(4):629
To compare the effects of two nap opportunities (20 and 90 min) to countermeasure the transient naturally occurring increased sleepiness and decreased performances during the post-lunch dip (PLD). Fourteen highly trained judokas completed in a counterbalanced and randomized order three test sessions (control (No-nap), 20- (N20) and 90-min (N90) nap opportunities). Test sessions consisted of the running-based anaerobic sprint test (RAST), simple and multiple-choice reaction times (MCRT) and the Epworth sleepiness scale (ESS). From the RAST, the maximum (Pmax), mean (Pmean) and minimum (Pmin) powers were calculated. Blood samples were taken before and after the RAST to measure the effect of pre-exercise napping on energetic and muscle damage biomarkers and antioxidant defense. N20 increased Pmax and Pmean compared to No-nap (p < 0.001, d = 0.59; d = 0.66) and N90 (p < 0.001, d = 0.98; d = 0.72), respectively. Besides, plasma lactate and creatinine increased only when the exercise was performed after N20. Both N20 (p < 0.001, d = 1.18) and N90 (p < 0.01, d = 0.78) enhanced post-exercise superoxide dismutase activity compared to No-nap. However, only N20 enhanced post-exercise glutathione peroxidase activity (p < 0.001, d = 1.01) compared to pre-nap. Further, MCRT performance was higher after N20 compared to No-nap and N90 (p < 0.001, d = 1.15; d = 0.81, respectively). Subjective sleepiness was lower after N20 compared to No-nap (p < 0.05, d = 0.92) and N90 (p < 0.01, d = 0.89). The opportunity to nap for 20 min in the PLD enhanced RAST, MCRT performances, and antioxidant defense, and decreased sleepiness. However, the opportunity of 90 min nap was associated with decreased repeated sprint performances and increased sleepiness, probably because of the sleep inertia. 相似文献
57.
NAD(P)H oxidase Nox-4 mediates 7-ketocholesterol-induced endoplasmic reticulum stress and apoptosis in human aortic smooth muscle cells 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Pedruzzi E Guichard C Ollivier V Driss F Fay M Prunet C Marie JC Pouzet C Samadi M Elbim C O'dowd Y Bens M Vandewalle A Gougerot-Pocidalo MA Lizard G Ogier-Denis E 《Molecular and cellular biology》2004,24(24):10703-10717
The mechanisms involved in the cytotoxic action of oxysterols in the pathogenesis of atherosclerosis still remain poorly understood. Among the major oxysterols present in oxidized low-density lipoprotein, we show here that 7-ketocholesterol (7-Kchol) induces oxidative stress and/or apoptotic events in human aortic smooth muscle cells (SMCs). This specific effect of 7-Kchol is mediated by a robust upregulation (threefold from the basal level) of Nox-4, a reactive oxygen species (ROS)-generating NAD(P)H oxidase homologue. This effect was highlighted by silencing Nox-4 expression with a specific small interfering RNA, which significantly reduced the 7-Kchol-induced production of ROS and abolished apoptotic events. Furthermore, the 7-Kchol activating pathway included an early triggering of endoplasmic reticulum stress, as assessed by transient intracellular Ca(2+) oscillations, and the induction of the expression of the cell death effector CHOP and of GRP78/Bip chaperone via the activation of IRE-1, all hallmarks of the unfolded protein response (UPR). We also showed that 7-Kchol activated the IRE-1/Jun-NH(2)-terminal kinase (JNK)/AP-1 signaling pathway to promote Nox-4 expression. Silencing of IRE-1 and JNK inhibition downregulated Nox-4 expression and subsequently prevented the UPR-dependent cell death induced by 7-Kchol. These findings demonstrate that Nox-4 plays a key role in 7-Kchol-induced SMC death, which is consistent with the hypothesis that Nox-4/oxysterols are involved in the pathogenesis of atherosclerosis. 相似文献
58.
Gfesser GA Zhang H Dinges J Fox GB Pan JB Esbenshade TA Yao BB Witte D Miller TR Kang CH Krueger KM Bennani YL Hancock AA Faghih R 《Bioorganic & medicinal chemistry letters》2004,14(3):673-676
Further SAR studies on novel histamine H(3) receptor antagonists are presented. Compound 14bb is a potent antagonist of both the rat cortical and human clone receptors, and is demonstrated to act functionally as an antagonist in an in vivo mouse dipsogenia model. 相似文献
59.
AIMS: The present work aims to study a new chitinase from Bacillus thuringiensis subsp. kurstaki. METHODS AND RESULTS: BUPM255 is a chitinase-producing strain of B. thuringiensis, characterized by its high chitinolytic and antifungal activities. The cloning and sequencing of the corresponding gene named chi255 showed an open reading frame of 2031 bp, encoding a 676 amino acid residue protein. Both nucleotide and amino acid sequences similarity analyses revealed that the chi255 is a new chitinase gene, presenting several differences from the published chi genes of B. thuringiensis. The identification of chitin hydrolysis products resulting from the activity, exhibited by Chi255 through heterologous expression in Escherichia coli revealed that this enzyme is a chitobiosidase. CONCLUSIONS: Another chitinase named Chi255 belonging to chitobiosidase class was evidenced in B. thuringiensis subsp. kurstaki and was shown to present several differences in its amino acid sequence with those of published ones. The functionality of Chi255 was proved by the heterologous expression of chi255 in E. coli. SIGNIFICANCE AND IMPACT OF THE STUDY: The addition of the sequence of chi255 to the few sequenced B. thuringiensis chi genes might contribute to a better investigation of the chitinase 'structure-function' relation. 相似文献
60.
Gfesser GA Faghih R Bennani YL Curtis MP Esbenshade TA Hancock AA Cowart MD 《Bioorganic & medicinal chemistry letters》2005,15(10):2559-2563
An SAR study of histamine H3 receptor antagonists based on substituted (R)-2-methyl-1-[2-(5-phenyl-benzofuran-2-yl)-ethyl]-pyrrolidines is presented. 相似文献