全文获取类型
收费全文 | 610篇 |
免费 | 28篇 |
国内免费 | 1篇 |
专业分类
639篇 |
出版年
2022年 | 3篇 |
2021年 | 10篇 |
2019年 | 6篇 |
2018年 | 12篇 |
2017年 | 16篇 |
2016年 | 13篇 |
2015年 | 17篇 |
2014年 | 21篇 |
2013年 | 27篇 |
2012年 | 29篇 |
2011年 | 20篇 |
2010年 | 13篇 |
2009年 | 31篇 |
2008年 | 27篇 |
2007年 | 42篇 |
2006年 | 42篇 |
2005年 | 23篇 |
2004年 | 17篇 |
2003年 | 20篇 |
2002年 | 17篇 |
2001年 | 23篇 |
2000年 | 27篇 |
1999年 | 11篇 |
1998年 | 15篇 |
1997年 | 7篇 |
1996年 | 7篇 |
1995年 | 6篇 |
1994年 | 4篇 |
1992年 | 9篇 |
1991年 | 5篇 |
1990年 | 11篇 |
1989年 | 11篇 |
1988年 | 9篇 |
1987年 | 8篇 |
1986年 | 7篇 |
1985年 | 6篇 |
1984年 | 4篇 |
1982年 | 3篇 |
1979年 | 5篇 |
1977年 | 2篇 |
1976年 | 8篇 |
1975年 | 4篇 |
1974年 | 4篇 |
1973年 | 4篇 |
1972年 | 4篇 |
1971年 | 4篇 |
1970年 | 2篇 |
1969年 | 8篇 |
1968年 | 3篇 |
1967年 | 3篇 |
排序方式: 共有639条查询结果,搜索用时 15 毫秒
11.
Zingman LV Alekseev AE Bienengraeber M Hodgson D Karger AB Dzeja PP Terzic A 《Neuron》2001,31(2):233-245
ATP-sensitive potassium (K(ATP)) channels are bifunctional multimers assembled by an ion conductor and a sulfonylurea receptor (SUR) ATPase. Sensitive to ATP/ADP, K(ATP) channels are vital metabolic sensors. However, channel regulation by competitive ATP/ADP binding would require oscillations in intracellular nucleotides incompatible with cell survival. We found that channel behavior is determined by the ATPase-driven engagement of SUR into discrete conformations. Capture of the SUR catalytic cycle in prehydrolytic states facilitated pore closure, while recruitment of posthydrolytic intermediates translated in pore opening. In the cell, channel openers stabilized posthydrolytic states promoting K(ATP) channel activation. Nucleotide exchange between intrinsic ATPase and ATP/ADP-scavenging systems defined the lifetimes of specific SUR conformations gating K(ATP) channels. Signal transduction through the catalytic module provides a paradigm for channel/enzyme operation and integrates membrane excitability with metabolic cascades. 相似文献
12.
13.
A novel disorder caused by defective biosynthesis of N-linked oligosaccharides due to glucosidase I deficiency 总被引:11,自引:0,他引:11 下载免费PDF全文
De Praeter CM Gerwig GJ Bause E Nuytinck LK Vliegenthart JF Breuer W Kamerling JP Espeel MF Martin JJ De Paepe AM Chan NW Dacremont GA Van Coster RN 《American journal of human genetics》2000,66(6):1744-1756
Glucosidase I is an important enzyme in N-linked glycoprotein processing, removing specifically distal alpha-1,2-linked glucose from the Glc3Man9GlcNAc2 precursor after its en bloc transfer from dolichyl diphosphate to a nascent polypeptide chain in the endoplasmic reticulum. We have identified a glucosidase I defect in a neonate with severe generalized hypotonia and dysmorphic features. The clinical course was progressive and was characterized by the occurrence of hepatomegaly, hypoventilation, feeding problems, seizures, and fatal outcome at age 74 d. The accumulation of the tetrasaccharide Glc(alpha1-2)Glc(alpha1-3)Glc(alpha1-3)Man in the patient's urine indicated a glycosylation disorder. Enzymological studies on liver tissue and cultured skin fibroblasts revealed a severe glucosidase I deficiency. The residual activity was <3% of that of controls. Glucosidase I activities in cultured skin fibroblasts from both parents were found to be 50% of those of controls. Tissues from the patient subjected to SDS-PAGE followed by immunoblotting revealed strongly decreased amounts of glucosidase I protein in the homogenate of the liver, and a less-severe decrease in cultured skin fibroblasts. Molecular studies showed that the patient was a compound heterozygote for two missense mutations in the glucosidase I gene: (1) one allele harbored a G-->C transition at nucleotide (nt) 1587, resulting in the substitution of Arg at position 486 by Thr (R486T), and (2) on the other allele a T-->C transition at nt 2085 resulted in the substitution of Phe at position 652 by Leu (F652L). The mother was heterozygous for the G-->C transition, whereas the father was heterozygous for the T-->C transition. These base changes were not seen in 100 control DNA samples. A causal relationship between the alpha-glucosidase I deficiency and the disease is postulated. 相似文献
14.
15.
16.
Ning Sui Virginie Monnier Yuriy Zakharko Yann Chevolot Sergei Alekseev Jean-Marie Bluet Vladimir Lysenko Eliane Souteyrand 《Plasmonics (Norwell, Mass.)》2013,8(1):85-92
Gold@silica core–shell nanoparticles were prepared with various gold core diameters (ranging from 20 to 150 nm) and silica thicknesses (ranging from 10 to 30 nm). When the gold diameter is increased, the size dispersion became larger, leading to a broader plasmon band. Then, silicon carbide (SiC) nanoparticles were covalently immobilized onto silica to obtain hybrid (Au@SiO2) SiC nanoparticles. The absorption properties of these hybrid nanoparticles showed that an excess of SiC nanoparticles in the dispersion can be identified by a strong absorption in the UV region. Compared to SiC reference samples, a blue shift of the fluorescence emission, from 582 to 523 nm, was observed, which was previously attributed to the strong surface modification of SiC when immobilized onto silica. Finally, the influence of several elaboration parameters (gold diameter, silica thickness, SiC concentration) on fluorescence enhancement was investigated. It showed that the highest enhancements were obtained with 10 nm silica thickness, low concentration of SiC nanoparticles, and surprisingly, with a 20-nm gold core diameter. This last result could be attributed to the broad plasmon band of big gold colloids. In this case, SiC emission strongly overlapped gold absorption, leading to possible quenching of SiC fluorescence by energy transfer. 相似文献
17.
One of the functions of cytochrome c in living cells is the initiation of apoptosis by catalyzing lipid peroxidation in the inner mitochondrial membrane, which involves cytochrome c bound with acidic lipids, especially cardiolipin. In this paper the results of studies of cytochrome c-cardiolipin complex structure carried out by different authors mainly on unilamellar cardiolipin-containing phospholipid liposomes are critically analyzed. The principal conclusion from the published papers is that cytochrome c-cardiolipin complex is formed by attachment of a cytochrome c molecule to the membrane surface via electrostatic interactions and the subsequent penetration of one of the fatty-acid cardiolipin chains into the protein globule, this being associated with hydrophobic interactions that break the >Fe…S(Met80) coordinate bond and giving rise to appearance of cytochrome c peroxidase activity. Nevertheless, according to data obtained in our laboratory, cytochrome c and cardiolipin form spherical nanoparticles in which protein is surrounded by a monolayer of cardiolipin molecules. Under the action of cooperative forces, the protein in the globule expands greatly in volume, its conformation is modified, and the protein becomes a peroxidase. In extended membranes, such as giant monolayer liposomes, and very likely in biological membranes, the formation of nanospheres of cytochrome c-cardiolipin complex causes fusion of membrane sections and dramatic chaotization of the whole membrane structure. The subsequent disintegration of the outer mitochondrial membrane is accompanied by cytochrome c release from the mitochondria and triggering of a cascade of programmed cell death reactions. 相似文献
18.
19.
L V Zingman A E Alekseev D M Hodgson-Zingman A Terzic 《Journal of applied physiology》2007,103(5):1888-1893
The cardiovascular system operates under a wide scale of demands, ranging from conditions of rest to extreme stress. How the heart muscle matches rates of ATP production with utilization is an area of active investigation. ATP-sensitive potassium (K(ATP)) channels serve a critical role in the orchestration of myocardial energetic well-being. K(ATP) channel heteromultimers consist of inwardly-rectifying K(+) channel 6.2 and ATP-binding cassette sulfonylurea receptor 2A that translates local ATP/ADP levels, set by ATPases and phosphotransfer reactions, to the channel pore function. In cells in which the mobility of metabolites between intracellular microdomains is limited, coupling of phosphotransfer pathways with K(ATP) channels permits a high-fidelity transduction of nucleotide fluxes into changes in membrane excitability, matching energy demands with metabolic resources. This K(ATP) channel-dependent optimization of cardiac action potential duration preserves cellular energy balance at varying workloads. Mutations of K(ATP) channels result in disruption of the nucleotide signaling network and generate a stress-vulnerable phenotype with excessive susceptibility to injury, development of cardiomyopathy, and arrhythmia. Solving the mechanisms underlying the integration of K(ATP) channels into the cellular energy network will advance the understanding of endogenous cardioprotection and the development of strategies for the management of cardiovascular injury and disease progression. 相似文献
20.
Juan Manuel Herrero-Medrano Hendrik-Jan Megens Martien AM Groenen Mirte Bosse Miguel Pérez-Enciso Richard PMA Crooijmans 《BMC genomics》2014,15(1)