全文获取类型
收费全文 | 83630篇 |
免费 | 4715篇 |
国内免费 | 11篇 |
专业分类
88356篇 |
出版年
2021年 | 965篇 |
2020年 | 868篇 |
2019年 | 858篇 |
2018年 | 2278篇 |
2017年 | 2007篇 |
2016年 | 2702篇 |
2015年 | 3516篇 |
2014年 | 3654篇 |
2013年 | 4868篇 |
2012年 | 5706篇 |
2011年 | 5057篇 |
2010年 | 3267篇 |
2009年 | 2381篇 |
2008年 | 3951篇 |
2007年 | 3697篇 |
2006年 | 3658篇 |
2005年 | 3046篇 |
2004年 | 3061篇 |
2003年 | 2726篇 |
2002年 | 2501篇 |
2001年 | 2057篇 |
2000年 | 1925篇 |
1999年 | 1481篇 |
1998年 | 659篇 |
1997年 | 475篇 |
1996年 | 523篇 |
1992年 | 932篇 |
1991年 | 854篇 |
1990年 | 843篇 |
1989年 | 917篇 |
1988年 | 753篇 |
1987年 | 771篇 |
1986年 | 700篇 |
1985年 | 772篇 |
1984年 | 648篇 |
1983年 | 570篇 |
1982年 | 473篇 |
1979年 | 685篇 |
1978年 | 505篇 |
1977年 | 508篇 |
1975年 | 604篇 |
1974年 | 641篇 |
1973年 | 626篇 |
1972年 | 576篇 |
1971年 | 513篇 |
1970年 | 556篇 |
1969年 | 633篇 |
1968年 | 585篇 |
1967年 | 499篇 |
1966年 | 478篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
991.
Avila C R Cantón F Barnestein P Suárez MF Marraccini P Rey M Humara JM Ordás R M Cánovas F 《Physiologia plantarum》2001,112(3):388-396
992.
Stimulus-dependent control of inositol 1,4,5-trisphosphate-induced Ca(2+) oscillation frequency by the endoplasmic reticulum Ca(2+)-ATPase 下载免费PDF全文
In many cell types, receptor stimulation evokes cytosolic calcium oscillations with a frequency that depends on agonist dose. Previous studies demonstrated controversial effects of changing the activity of the endoplasmic reticulum Ca(2+)-ATPase upon the frequency of oscillations. By numerical simulations, we found that the model of De Young and Keizer (J. Keizer and G.W. De Young, 1994, J. Theor. Biol. 166: 431-442), unlike other models, can explain the observed discrepancies, assuming that the different experiments were performed at different stimulus levels. According to model predictions, partial inhibition of internal calcium pumps is expected to increase frequency at low stimulus strength and should have an opposite effect at strong stimuli. Similar results were obtained using an analytical estimation of oscillation period, based on calcium-dependent channel activation and inactivation. In experiments on HeLa cells, 4 nM thapsigargin increased the frequency of calcium oscillations induced by 1 and 2.5 microM histamine but had no effect on supramaximally stimulated cells. In HEp-2 cells, 2 nM thapsigargin slowed down the rapid, ATP-induced oscillations. Our results suggest that in the investigated cell types, the De Young-Keizer model based on inositol 1,4,5-trisphosphate-dependent calcium-induced calcium release can properly describe intracellular calcium oscillations. 相似文献
993.
Receptor-like properties of the 26 kDa transmembrane form of TNF 总被引:1,自引:0,他引:1
Most members of the TNF family of proteins exist as transmembrane proteins with relatively long intracellular domains, and a number of them are involved in the ill-defined phenomenon of "reverse signaling". We have identified a putative nuclear localization signal in the cytoplasmic domain of TNF which proved to be functional in two assays. Western analysis identified an approximately 10 kDa peptide corresponding to the transmembrane and cytoplasmic domains of TNF after the proteolytic liberation of the 17 kDa, soluble form of TNF. This 10 kDa peptide was enriched in internal membranes and nuclear fractions of disrupted cells. Immune electron-microscopic studies proved its localization in transport vesicles and the nucleus. The nuclear transport of the intracellular segment of TNF resembles the signaling process through the Notch-type of receptors. Indeed, the presence of the 10 kDa peptide seems to influence the expression of another inflammatory cytokine, interleukin-1 beta. These findings suggest that the transmembrane form of TNF has receptor-like properties and its interaction with the receptors initiates a bidirectional signaling. 相似文献
994.
I Kisfalvi G Rácz A Bálint M Máté A Oláh T Zelles E S Vizi G Varga 《Journal of Physiology》2001,95(1-6):385-389
Galanin is a neuropeptide having a wide range of biological actions. Recently selective galanin receptor antagonists such as M35 [galanin(1-12)-Pro-bradykinin(2-9)-amide] and C7 [galanin(1-12)-Pro-spantide-amide] have been described. These antagonists have blocked the actions of galanin on flexor reflex, glucose-induced insulin secretion, and acetyicholine release from hippocampus. Our present aim was to investigate whether M35 and C7 can affect galanin-induced inhibition of pancreatic enzyme secretion in rats. Pancreatic enzyme secretion was studied in urethane-anesthetized rats supplied with jugular vein catheter and pancreatic cannula. Amylase secretion evoked by submaximal CCK-8 stimulation was inhibited dose-dependently by galanin in anesthetized rats. Surprisingly, neither M35 nor C7 was able to inhibit the responses of the exocrine pancreas to galanin. However, both putative galanin receptor antagonists behaved as agonists in our experimental models. Our data suggest that the effects of galanin on pancreatic enzyme secretion are not mediated by M35- or C7-sensitive galanin receptors. Therefore, these galanin receptors are different from those described in the central nervous system. 相似文献
995.
High-frequency synaptic activity can cause facilitation of transmitter release due to accumulation of “residual Ca2+” at the nerve terminal. However, the mechanism of this phenomenon is still under debate. Here we show that, using extracellular recording from frog cutaneous pectoris muscle, paired-pulse facilitation (PPF) at the frog neuro-muscular junction decays in two or three-exponential manner depending upon the extracellular Ca2+ concentration ([Ca2+]e). First, second and “early” PPF components are analyzed and described in this study. Considering the dependence of PPF on [Ca2+]e, existence of several specific high-affinity intra-terminal Ca2+-binding sites that underlie the facilitation of transmitter release at the frog neuro-muscular junction is proposed. 相似文献
996.
A. Rubashkin P. Iserovich J.A. Hernández J. Fischbarg 《The Journal of membrane biology》2006,208(3):251-263
The purpose of the present work is to investigate whether the idea of epithelial fluid transport based on electro-osmotic
coupling at the level of the leaky tight junction (TJ) can be further supported by a plausible theoretical model. We develop
a model for fluid transport across epithelial layers based on electro-osmotic coupling at leaky tight junctions (TJ) possessing
protruding macromolecules and fixed electrical charges. The model embodies systems of electro-hydrodynamic equations for the
intercellular pathway, namely the Brinkman and the Poisson-Boltzmann differential equations applied to the TJ. We obtain analytical
solutions for a system of these two equations, and are able to derive expressions for the fluid velocity profile and the electrostatic
potential. We illustrate the model by employing geometrical parameters and experimental data from the corneal endothelium,
for which we have previously reported evidence for a central role for electro-osmosis in translayer fluid transport. Our results
suggest that electro-osmotic coupling at the TJ can account for fluid transport by the corneal endothelium. We conclude that
electro-osmotic coupling at the tight junctions could represent one of the basic mechanisms driving fluid transport across
some leaky epithelia, a process that remains unexplained. 相似文献
997.
Sanz-González SM Melero-Fernández de Mera R Malek NP Andrés V 《Journal of cellular biochemistry》2006,97(4):735-743
Excessive cellular proliferation is thought to contribute to neointimal lesion development during atherosclerosis and restenosis after angioplasty. Inhibition of cyclin-dependent kinase (CDK) activity by p27 inhibits mammalian cell growth. Mounting evidence indicates that p27 negatively regulates neointimal thickening in animal models of restenosis and atherosclerosis, and its expression in human neointimal lesions is consistent with such a protective role. Cell cycle progression is facilitated by cyclinE/CDK2-dependent phosphorylation of p27 on threonine 187 (T187) during late G1. The purpose of this study was to assess whether this phosphorylation event plays a role during atherosclerosis. To this end, we generated apolipoprotein E-null mice with both p27 alleles replaced by a mutated form non-phosphorylatable at T187 (apoE-/-p27T187A mice) and investigated the kinetics of atheroma development in these animals compared to apoE-/- controls with an intact p27 gene. Fat feeding resulted in comparable level of hypercholesterolemia in both groups of mice. Surprisingly, aortic p27 expression was not increased in fat-fed apoE-/-p27T187A mice compared with apoE-/- controls. Moreover, atheroma size, lesion cellularity, proliferation, and apoptotic rates were undistinguishable in both groups of fat-fed mice. Thus, in contrast to previous studies that highlight the importance of p27 phosphorylation at T187 on the control of p27 expression and function in different tissues and pathophysiological scenarios, our findings demonstrate that this phosphorylation event is not implicated in the control of aortic p27 expression and atheroma progression in hypercholesterolemic mice. 相似文献
998.
999.
1000.
Proton magnetic resonance study of lysine-binding to the kringle 4 domain of human plasminogen. The structure of the binding site 总被引:2,自引:0,他引:2
The binding of L-Lys, D-Lys and epsilon-aminocaproic acid (epsilon ACA) to the kringle 4 domain of human plasminogen has been investigated via one and two-dimensional 1H-nuclear magnetic resonance spectroscopy at 300 and 600 MHz. Ligand-kringle association constants (Ka) were determined assuming single site binding. At 295 K, pH 7.2, D-Lys binds to kringle 4 much more weakly (Ka = 1.2 mM-1) than does L-Lys (Ka = 24.4 mM-1). L-Lys binding to kringle 4 causes the appearance of ring current-shifted high-field resonances within the -1 approximately less than delta approximately less than 0 parts per million range. The ligand origin of these signals has been confirmed by examining the spectra of kringle 4 titrated with deuterated L-Lys. A systematic analysis of ligand-induced shifts on the aromatic resonances of kringle 4 has been carried out on the basis of 300 MHz two-dimensional chemical shift correlated (COSY) and double quantum correlated spectroscopies. Significant differences in the effect of L-Lys and D-Lys binding to kringle 4 have been observed in the aromatic COSY spectrum. In particular, the His31 H4 and Trp72 H2 singlets and the Phe64 multiplets appear to be the most sensitive to the particular enantiomers, indicating that these residues are in proximity to the ligand C alpha center. In contrast, the rest of the indole spectrum of Trp72 and the aromatic resonances of Trp62 and Tyr74, which are affected by ligand presence, are insensitive to the optical nature of the ligand isomer. These results, together with two-dimensional proton Overhauser studies and ligand-kringle saturation transfer experiments reported previously, enabled us to generate a model of the kringle 4 ligand-binding site from the crystallographic co-ordinates of the prothrombin kringle 1. The latter, although lacking recognizable lysine-binding capability, is otherwise structurally homologous to the plasminogen kringles. 相似文献