全文获取类型
收费全文 | 2964篇 |
免费 | 183篇 |
专业分类
3147篇 |
出版年
2023年 | 14篇 |
2022年 | 39篇 |
2021年 | 56篇 |
2020年 | 35篇 |
2019年 | 75篇 |
2018年 | 70篇 |
2017年 | 53篇 |
2016年 | 89篇 |
2015年 | 164篇 |
2014年 | 140篇 |
2013年 | 208篇 |
2012年 | 243篇 |
2011年 | 210篇 |
2010年 | 136篇 |
2009年 | 102篇 |
2008年 | 173篇 |
2007年 | 180篇 |
2006年 | 169篇 |
2005年 | 162篇 |
2004年 | 158篇 |
2003年 | 132篇 |
2002年 | 151篇 |
2001年 | 23篇 |
2000年 | 19篇 |
1999年 | 28篇 |
1998年 | 21篇 |
1997年 | 20篇 |
1996年 | 23篇 |
1995年 | 20篇 |
1994年 | 16篇 |
1993年 | 14篇 |
1992年 | 12篇 |
1991年 | 19篇 |
1990年 | 9篇 |
1989年 | 9篇 |
1988年 | 10篇 |
1987年 | 12篇 |
1986年 | 6篇 |
1985年 | 6篇 |
1984年 | 12篇 |
1983年 | 10篇 |
1982年 | 21篇 |
1981年 | 9篇 |
1980年 | 7篇 |
1979年 | 9篇 |
1978年 | 5篇 |
1977年 | 10篇 |
1976年 | 5篇 |
1975年 | 4篇 |
1971年 | 4篇 |
排序方式: 共有3147条查询结果,搜索用时 15 毫秒
911.
912.
Micheli F Fabio RD Cavanni P Rimland JM Capelli AM Chiamulera C Corsi M Corti C Donati D Feriani A Ferraguti F Maffeis M Missio A Ratti E Paio A Pachera R Quartaroli M Reggiani A Sabbatini FM Trist DG Ugolini A Vitulli G 《Bioorganic & medicinal chemistry》2003,11(2):171-183
Metabotropic glutamate receptors (mGluRs) are an unusual family of G-protein coupled receptor (GPCR), and are characterised by a large extracellular N-terminal domain that contains the glutamate binding site. We have identified a new class of non-competitive metabotropic glutamate receptor 1 (mGluR1) antagonists, 2,4-dicarboxy-pyrroles which are endowed with nanomolar potency. They interact within the 7 transmembrane (7TM) domain of the receptor and show antinociceptive properties when tested in a number of different animal models. 相似文献
913.
A balance of capping protein and profilin functions is required to regulate actin polymerization in Drosophila bristle 下载免费PDF全文
Profilin is a well-characterized protein known to be important for regulating actin filament assembly. Relatively few studies have addressed how profilin interacts with other actin-binding proteins in vivo to regulate assembly of complex actin structures. To investigate the function of profilin in the context of a differentiating cell, we have studied an instructive genetic interaction between mutations in profilin (chickadee) and capping protein (cpb). Capping protein is the principal protein in cells that caps actin filament barbed ends. When its function is reduced in the Drosophila bristle, F-actin levels increase and the actin cytoskeleton becomes disorganized, causing abnormal bristle morphology. chickadee mutations suppress the abnormal bristle phenotype and associated abnormalities of the actin cytoskeleton seen in cpb mutants. Furthermore, overexpression of profilin in the bristle mimics many features of the cpb loss-of-function phenotype. The interaction between cpb and chickadee suggests that profilin promotes actin assembly in the bristle and that a balance between capping protein and profilin activities is important for the proper regulation of F-actin levels. Furthermore, this balance of activities affects the association of actin structures with the membrane, suggesting a link between actin filament dynamics and localization of actin structures within the cell. 相似文献
914.
915.
Epidemiological data from retrospective and case-control studies have indicated that estrogen replacement therapy can decrease the risk of developing Alzheimer's disease. In addition, estrogen replacement therapy has been found to promote neuronal survival both in vivo and in vitro. We have shown that conjugated equine estrogens (CEE), containing 238 different molecules composed of estrogens, progestins, and androgens, exerted neurotrophic and neuroprotective effects in cultured neurons. In the current study, we sought to determine whether a steroidal formulation of nine synthetic conjugated estrogens (SCE) chemically derived from soybean and yam extracts is as effective as the complex multisteroidal formulation of CEE. Analyses of the neuroprotective efficacy indicate that SCE exhibited significant neuroprotection against beta amyloid, hydrogen peroxide, and glutamate-induced toxicity in cultured hippocampal neurons. Indices of neuroprotection included an increase in neuronal survival, a decrease in neurotoxin-induced lactate dehydrogenase release, and a reduction in neurotoxin-induced apoptotic cell death. Furthermore, SCE was found to attenuate excitotoxic glutamate-induced [Ca2+]i rise. Quantitative analyses indicate that the neuroprotective efficacy of SCE was comparable to that of the multisteroidal CEE formulation. Data derived from these investigations predict that SCE could exert neuroprotective effects comparable to CEE in vivo and therefore could reduce the risk of Alzheimer's disease in postmenopausal women. 相似文献
916.
917.
The effects of taking into account in a perfect integrate and fire model of neuronal activity the spatial localization of the synapses are studied by superposing to the diffusion a simple discrete jump component. Different criteria are employed to assess the role of excitatory and inhibitory discrete contributions. Comparisons are performed with respect to the case where contributions coming from synapses more distal from the trigger zone are summed up in a continuous model. A systematic study of the output frequency and of the inter spike interval coefficient of variation (CV) is performed by means of examples as the model parameters are varied. 相似文献
918.
Naughton P Foresti R Bains SK Hoque M Green CJ Motterlini R 《The Journal of biological chemistry》2002,277(43):40666-40674
Nitric oxide and S-nitrosothiols modulate a variety of important physiological activities. In vascular cells, agents that release NO and donate nitrosonium cation (NO(+)), such as S-nitrosoglutathione, are potent inducers of the antioxidant protein heme oxygenase 1 (HO-1) (Foresti, R., Clark, J. E., Green, C. J., and Motterlini, R. (1997) J. Biol. Chem. 272, 18411-18417; Motterlini, R., Foresti, R., Bassi, R., Calabrese, V., Clark, J. E., and Green, C. J. (2000) J. Biol. Chem. 275, 13613-13620). Here, we report that Angeli's salt (AS) (0.25-2 mm), a compound that releases nitroxyl anion (NO(-)) at physiological pH, induces HO-1 mRNA and protein expression in a concentration- and time-dependent manner, resulting in increased heme oxygenase activity in rat H9c2 cells. A time course analysis revealed that NO(-)-mediated HO-1 expression is transient and gradually disappears within 24 h, in accordance with the short half-life of AS at 37 degrees C (t(12) = 2.3 min). Interestingly, multiple additions of AS at lower concentrations (50 or 100 microm) over a period of time still promoted a significant increase in heme oxygenase activity. Experiments performed using a NO scavenger and the NO electrode confirmed that NO(-), not NO, is the species involved in HO-1 induction by AS; however, the effect on heme oxygenase activity can be amplified by accelerating the rate of NO(-) oxidation. N-Acetylcysteine almost completely abolished AS-mediated induction of HO-1, whereas a glutathione synthesis inhibitor (buthionine sulfoximine) significantly decreased heme oxygenase activation by AS, indicating that sulfydryl groups are crucial targets in the regulation of HO-1 expression by NO(-). We conclude that NO(-), in analogy with other reactive nitrogen species, is a potent inducer of heme oxygenase activity and HO-1 protein expression. These findings indicate that heme oxygenase can act both as a sensor to and target of redox-based mechanisms involving NO and extend our knowledge on the biological function of HO-1 in response to nitrosative stress. 相似文献
919.
Ceccarelli C Grodsky NB Ariyaratne N Colman RF Bahnson BJ 《The Journal of biological chemistry》2002,277(45):43454-43462
The crystal structure of porcine heart mitochondrial NADP+-dependent isocitrate dehydrogenase (IDH) complexed with Mn2+ and isocitrate was solved to a resolution of 1.85 A. The enzyme was expressed in Escherichia coli, purified as a fusion protein with maltose binding protein, and cleaved with thrombin to yield homogeneous enzyme. The structure was determined by multiwavelength anomalous diffraction phasing using selenium substitution in the form of selenomethionine as the anomalous scatterer. The porcine NADP+-IDH enzyme is structurally compared with the previously solved structures of IDH from E. coli and Bacillus subtilis that share 16 and 17% identity, respectively, with the mammalian enzyme. The porcine enzyme has a protein fold similar to the bacterial IDH structures with each monomer folding into two domains. However, considerable differences exist between the bacterial and mammalian forms of IDH in regions connecting core secondary structure. Based on the alignment of sequence and structure among the porcine, E. coli, and B. subtilis IDH, a putative phosphorylation site has been identified for the mammalian enzyme. The active site, including the bound Mn2+-isocitrate complex, is highly ordered and, therefore, mechanistically informative. The consensus IDH mechanism predicts that the Mn2+-bound hydroxyl of isocitrate is deprotonated prior to its NADP+-dependent oxidation. The present crystal structure has an active site water that is well positioned to accept the proton and ultimately transfer the proton to solvent through an additional bound water. 相似文献
920.
Carotenoid concentration in barn swallow eggs is influenced by laying order,maternal infection and paternal ornamentation 总被引:19,自引:0,他引:19
Saino N Bertacche V Ferrari RP Martinelli R Møller AP Stradi R 《Proceedings. Biological sciences / The Royal Society》2002,269(1501):1729-1733
Carotenoids are critical to embryonic development, immunity and protection from oxidative stress. Transmission of carotenoids to the eggs may affect development and maturation of immunity in offspring, but carotenoids may be available to females in limiting amounts. Females may thus transfer carotenoids to the eggs differentially in relation to the reproductive value of the offspring as affected by sexual ornamentation of their father. In this study of maternal allocation of carotenoids to the eggs in the barn swallow (Hirundo rustica), females whose immune system had been experimentally challenged with an antigen had smaller lutein concentrations in their eggs than controls. We manipulated the size of a secondary sexual character (tail length) of males, and analysed the effect of manipulation on allocation of lutein to eggs by their vaccinated mates. Contrary to our prediction based on parental allocation theory, mates of tail-shortened males had a larger lutein concentration in their eggs compared with those of control and tail-elongated males. According to previous studies, offspring of short-tailed males have larger exposure and/or susceptibility to parasites. A larger lutein concentration in the eggs of females mated to males with experimentally reduced ornaments may thus reflect adaptive maternal strategies to enhance offspring viability. 相似文献