全文获取类型
收费全文 | 430篇 |
免费 | 37篇 |
专业分类
467篇 |
出版年
2022年 | 4篇 |
2021年 | 5篇 |
2020年 | 4篇 |
2019年 | 4篇 |
2017年 | 7篇 |
2016年 | 13篇 |
2015年 | 13篇 |
2014年 | 7篇 |
2013年 | 12篇 |
2012年 | 17篇 |
2011年 | 20篇 |
2010年 | 12篇 |
2009年 | 8篇 |
2008年 | 15篇 |
2007年 | 10篇 |
2006年 | 18篇 |
2005年 | 12篇 |
2004年 | 8篇 |
2003年 | 12篇 |
2002年 | 15篇 |
2001年 | 6篇 |
2000年 | 7篇 |
1999年 | 6篇 |
1995年 | 8篇 |
1993年 | 3篇 |
1992年 | 17篇 |
1991年 | 9篇 |
1990年 | 17篇 |
1989年 | 8篇 |
1988年 | 14篇 |
1987年 | 8篇 |
1986年 | 13篇 |
1985年 | 9篇 |
1984年 | 13篇 |
1983年 | 10篇 |
1982年 | 6篇 |
1981年 | 6篇 |
1980年 | 6篇 |
1979年 | 8篇 |
1978年 | 9篇 |
1977年 | 7篇 |
1976年 | 5篇 |
1975年 | 8篇 |
1974年 | 7篇 |
1973年 | 10篇 |
1972年 | 4篇 |
1971年 | 3篇 |
1970年 | 3篇 |
1969年 | 3篇 |
1968年 | 3篇 |
排序方式: 共有467条查询结果,搜索用时 0 毫秒
111.
Synucleinopathies such as Parkinson's disease, multiple system atrophy and dementia with Lewy bodies are characterized by deposition of aggregated α-synuclein. Recent findings indicate that pathological oligomers rather than fibrillar aggregates may represent the main toxic protein species. It has been shown that α-synuclein oligomers can increase the conductance of lipid bilayers and, in cell-culture, lead to calcium dyshomeostasis and cell death. In this study, employing a setup for single-channel electrophysiology, we found that addition of iron-induced α-synuclein oligomers resulted in quantized and stepwise increases in bilayer conductance indicating insertion of distinct transmembrane pores. These pores switched between open and closed states depending on clamped voltage revealing a single-pore conductance comparable to that of bacterial porins. Pore conductance was dependent on transmembrane potential and the available cation. The pores stably inserted into the bilayer and could not be removed by buffer exchange. Pore formation could be inhibited by co-incubation with the aggregation inhibitor baicalein. Our findings indicate that iron-induced α-synuclein oligomers can form a uniform and distinct pore species with characteristic electrophysiological properties. Pore formation could be a critical event in the pathogenesis of synucleinopathies and provide a novel structural target for disease-modifying therapy. 相似文献
112.
van Haperen R van Tol A van Gent T Scheek L Visser P van der Kamp A Grosveld F de Crom R 《The Journal of biological chemistry》2002,277(50):48938-48943
Plasma phospholipid transfer protein (PLTP) is thought to be involved in the remodeling of high density lipoproteins (HDL), which are atheroprotective. It is also involved in the metabolism of very low density lipoproteins (VLDL). Hence, PLTP is thought to be an important factor in lipoprotein metabolism and the development of atherosclerosis. We have overexpressed PLTP in mice heterozygous for the low density lipoprotein (LDL) receptor, a model for atherosclerosis. We show that increased PLTP activity results in a dose-dependent decrease in HDL, and a moderate stimulation of VLDL secretion (=1.5-fold). The mice were given a high fat, high cholesterol diet, which resulted in hypercholesterolemia in all animals. HDL concentrations were dramatically reduced in PLTP-overexpressing animals when compared with LDL receptor controls, whereas VLDL + LDL cholesterol levels were identical. Susceptibility to atherosclerosis was increased in a PLTP dose-responsive manner. We conclude that PLTP increases susceptibility to atherosclerosis by lowering HDL concentrations, and therefore we suggest that an increase in PLTP is a novel, long term risk factor for atherosclerosis in humans. 相似文献
113.
114.
115.
Involvement of the hydrophobic patch of azurin in the electron-transfer reactions with cytochrome C551 and nitrite reductase 总被引:2,自引:0,他引:2
M van de Kamp M C Silvestrini M Brunori J Van Beeumen F C Hali G W Canters 《European journal of biochemistry》1990,194(1):109-118
The electron-transfer reactions of site-specific mutants of the blue copper protein azurin from Pseudomonas aeruginosa with its presumed physiological redox partners cytochrome c551 and nitrite reductase were investigated by temperature-jump and stopped-flow experiments. In the hydrophobic patch of azurin Met44 was replaced by Lys, and in the His35 patch His35 was replaced by Phe, Leu and Gln. Both patches were previously thought to be involved in electron transfer. 1H-NMR spectroscopy revealed only minor changes in the three-dimensional structure of the mutants compared to wild-type azurin. Observed changes in midpoint potentials could be attributed to electrostatic effects. The slow relaxation phase observed in temperature-jump experiments carried out on equilibrium mixtures of wild-type azurin and cytochrome c551 was definitively shown to be due to a conformational relaxation involving His35. Analysis of the kinetic data demonstrated the involvement of the hydrophobic but not the His35 patch of azurin in the electron transfer reactions with both cytochrome c551 and nitrite reductase. 相似文献
116.
Background
Interaction graphs (signed directed graphs) provide an important qualitative modeling approach for Systems Biology. They enable the analysis of causal relationships in cellular networks and can even be useful for predicting qualitative aspects of systems dynamics. Fundamental issues in the analysis of interaction graphs are the enumeration of paths and cycles (feedback loops) and the calculation of shortest positive/negative paths. These computational problems have been discussed only to a minor extent in the context of Systems Biology and in particular the shortest signed paths problem requires algorithmic developments. 相似文献117.
Phospholipid uptake by Plasmodium knowlesi infected erythrocytes 总被引:2,自引:0,他引:2
G N Moll H J Vial M L Ancelin J A Op den Kamp B Roelofsen L L van Deenen 《FEBS letters》1988,232(2):341-346
The uptake of phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylserine (PS) in Plasmodium knowlesi infected erythrocytes has been studied. Whereas uptake of phospholipids, in the absence of phospholipid transfer proteins, is negligible in control cells, the infected cells can incorporate considerable amounts of added phospholipids. The uptake is enhanced by the presence of lipid transfer proteins. Doubly labeled [3H]oleate, [14C]choline) PC does not undergo any appreciable remodelling following uptake, which strongly suggests that plasma PC is used as such for the biogenesis of the parasite membranes. Transport of extracellularly offered PS and PE towards the intraerythrocytic parasite and utilization of these lipids by the parasite are confirmed by the observation that these lipids are converted into respectively PE and PC. The extent and rate of these conversions depend on the way the phospholipids are introduced into the infected cells. 相似文献
118.
Brinkman-Van der Linden Els C.M.; Havenaar Ellen C.; Van Ommen Esther C.R.; Van Kamp Gerard J.; Gooren Louis J.G.; Van Dijk Willem 《Glycobiology》1996,6(4):407-412
The effect of estrogen on the glycosylation of 相似文献
119.
120.
G N Moll V van den Eertwegh H Tournois B Roelofsen J A Op den Kamp L L van Deenen 《Biochimica et biophysica acta》1991,1062(2):206-210
We studied the differential effect of tryptophan-N-formylated gramicidin on uninfected and Plasmodium falciparum-infected erythrocytes. Trp-N-formylated gramicidin induces a much faster leakage of K+ from infected cells than from uninfected cell whereas, and at an even lower concentration, gramicidin A' causes a rapid K+ leakage from both uninfected and infected cells. We also studied the effect of Trp-N-formylated gramicidin and gramicidin A' incorporated in liposomes on the growth of Plasmodium falciparum in an in vitro culture. Incorporation of Trp-N-formylated gramicidin in the membranes of so-called 'stealth' vesicles strongly decreases the concentration needed to induce 50% inhibition of parasite growth. Moreover, no decrease in the K+ content of uninfected cells was observed when cells were exposed to liposome-incorporated Trp-N-formylated gramicidin at a concentration which causes full inhibition of parasite growth. These observations strongly suggest that Trp-N-formylated gramicidin incorporated in 'stealth' vesicles ends up specifically in the infected cell, thereby inhibiting the growth of the growth of the malaria parasite. 相似文献