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211.
Buchanan MS Carroll AR Fechner GA Boyle A Simpson MM Addepalli R Avery VM Hooper JN Su N Chen H Quinn RJ 《Bioorganic & medicinal chemistry letters》2007,17(24):6860-6863
Isoprenylcysteine methyltransferase (Icmt) catalyzes the carboxyl methylation of oncogenic proteins in the final step of a series of post-translational modifications. The inhibition of Icmt provides an attractive and novel anticancer target. A natural product high-throughput screening campaign was conducted to discover inhibitors of Icmt. The Australian marine sponge, Pseudoceratina sp., yielded spermatinamine, a novel alkaloid with a bromotyrosyl-spermine-bromotyrosyl sequence, as the bioactive constituent. Its structure was determined by 1D and 2D NMR spectroscopy. Spermatinamine is the first natural product inhibitor of Icmt. 相似文献
212.
Van Camp JA Hu LY Kostlan C Lefker B Li J Mitchell L Wang Z Yue WS Carroll M Dettling D Du D Pocalyko D Wade K 《Bioorganic & medicinal chemistry letters》2007,17(20):5529-5532
A series of substituted 4-aryl-2-trifluoromethylbenzonitrile analogs were evaluated in the human androgen receptor binding and cellular functional assays. Analogs with sufficient in vitro binding and cellular potency (IC(50)<200 nM) were tested in the progesterone receptor binding assay for selectivity and in the Golden Syrian hamster ear model for in vivo efficacy. Within the series, compound 4 e was identified to be the most active analog in vivo (wax ester inhibition=86%). 相似文献
213.
Expression of Mycobacterium tuberculosis Rv1991c using an arabinose-inducible promoter demonstrates its role as a toxin 总被引:1,自引:0,他引:1
Conditional gene expression systems are useful tools for studying the role of essential or toxic gene products in bacterial systems. There is a paucity of such systems available for use in the mycobacteria. The utility of the Escherichia coli arabinose-inducible system was looked into, since it is tightly controlled in response to the presence of arabinose and glucose. It was demonstrated that the P(BAD) promoter can be used to express heterologous genes in Mycobacterium smegmatis. Expression of a lacZ reporter gene demonstrated that promoter activity was inducible in response to the presence of glucose, but only on solid medium. This system was utilized to study the functional consequences of expressing one member of a putative toxin-antitoxin pair (Rv1991c). Rv1991c has homology with a number of bacterial toxins, including ChpK, MazF and PemK. A potential antitoxin gene has been identified, adjacent to Rv1991c in the genome, which was coexpressed with the toxin. Expression of the toxin alone inhibited the growth of E. coli, whereas coexpression with the antitoxin did not. Expression of Rv1991c also led to a marked reduction of cell viability in M. smegmatis, confirming its role as a potent toxin. 相似文献
214.
R Moriggi Jr HS Di Mauro SC Dias JM Matos MB Urtado NF Camar?o IV Sousa Neto DC Nascimento RA Tibana CO Assump??o J Prestes CB Urtado 《Biology of sport / Institute of Sport》2015,32(4):289-294
Low intensity resistance exercise (RE) with blood flow restriction (BFR) has gained attention in the literature due to the beneficial effects on functional and morphological variables, similar to those observed during traditional RE without BFR, while the effects of BFR on post-exercise hypotension remain unclear. The aim of the present study was to compare the blood pressure (BP) response of trained normotensive individuals to RE with and without BFR. In this cross-over randomized trial, eight male subjects (23.8 ± 4 years, 74 ± 3 kg, 174 ± 4 cm) completed two exercise protocols: traditional RE (3 x 10 repetitions at 70% one-repetition maximum [1-RM]) and low intensity RE (3 x 15 repetitions at 20% 1-RM) with BFR. Blood pressure measurements were performed after 15 min of seated rest (0), immediately after and 10 min, 20 min, 30 min, 40 min, 50 min and 60 min after the experimental sessions. Similar hypotensive effects for systolic BP (SBP) were observed for both protocols (P < 0.05) after exercise, with no differences between groups (P > 0.05) and no statistically significant difference for diastolic BP (P > 0.05). These results suggest that in normotensive trained individuals, both traditional RE and RE with BFR induce hypotension for SBP, which is important to prevent cardiovascular disturbances. 相似文献
215.
JY Xiong SC Li YX Sun XS Zhang ZZ Dong P Zhong XR Sun 《Biology of sport / Institute of Sport》2015,32(4):295-300
Increasing evidence suggests that physical activity could delay or attenuate the symptoms of Alzheimer''s disease (AD). But the underlying mechanisms are still not fully understood. To investigate the effect of long-term treadmill exercise on the spatial memory of AD mice and the possible role of β-amyloid, brain-derived neurotrophic factor (BDNF) and microglia in the effect, male APPswe/PS1dE9 AD mice aged 4 months were subjected to treadmill exercise for 5 months with 6 sessions per week and gradually increased load. A Morris water maze was used to evaluate the spatial memory. Expression levels of β-amyloid, BDNF and Iba-1 (a microglia marker) in brain tissue were detected by immunohistochemistry. Sedentary AD mice and wildtype C57BL/6J mice served as controls. The results showed that 5-month treadmill exercise significantly decreased the escape latencies (P < 0.01 on the 4th day) and improved the spatial memory of the AD mice in the water maze test. Meanwhile, treadmill exercise significantly increased the number of BDNF-positive cells and decreased the ratios of activated microglia in both the cerebral cortex and the hippocampus. However, treadmill exercise did not significantly alleviate the accumulation of β-amyloid in either the cerebral cortex or the hippocampus of the AD mice (P > 0.05). The study suggested that long-term treadmill exercise could improve the spatial memory of the male APPswe/PS1dE9 AD mice. The increase in BDNF-positive cells and decrease in activated microglia might underpin the beneficial effect. 相似文献
216.
Jean-Marie Burel Sébastien Besson Colin Blackburn Mark Carroll Richard K. Ferguson Helen Flynn Kenneth Gillen Roger Leigh Simon Li Dominik Lindner Melissa Linkert William J. Moore Balaji Ramalingam Emil Rozbicki Aleksandra Tarkowska Petr Walczysko Chris Allan Josh Moore Jason R. Swedlow 《Mammalian genome》2015,26(9-10):441-447
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219.
Although substantial advances have been made in behavioral and pharmacological treatments for addictions, moving treatment development to the next stage may require novel ways of approaching addictions, particularly ways based on new findings regarding the neurobiological underpinnings of addictions that also assimilate and incorporate relevant information from earlier approaches. In this review, we first briefly review theoretical and biological models of addiction and then describe existing behavioral and pharmacologic therapies for the addictions within this framework. We then propose new directions for treatment development and targets that are informed by recent evidence regarding the heterogeneity of addictions and the neurobiological contributions to these disorders. 相似文献
220.
Haave M Folven KI Carroll T Glover C Heegaard E Brattelid T Hogstrand C Lundebye AK 《Cell biology and toxicology》2011,27(5):343-361
Nutrients in seafood are known to be beneficial for brain development. Effects of maternal exposure to 2,2′,4,4′ tetrabromo
diphenylether (BDE47) was investigated, alongside the potential ameliorating impact of seafood nutrients, through assessment
of neurobehaviour and gene expression in brain and liver. Developing mice were exposed during gestation and lactation via
dams dosed through casein- or salmon-based feed, spiked with BDE47. Two concentrations were used: a low level (6 μg/kg feed)
representing an environmentally realistic concentration and a high level (1,900 μg/kg feed) representing a BDE47 intake much
higher than expected from frequents consumption of contaminated seafood. Experimental groups were similar with respect to
reproductive success, growth and physical development. Minor, transient changes in neurobehavioural metrics were observed
in groups given the highest dose of BDE47. No significant differences in behaviour or development were seen on postnatal day 18
among maternally exposed offspring. Cerebral gene expression investigated by microarray analyses and validated by RT-qPCR
showed low fold changes for all genes, despite dose-dependent accumulation of BDE47 in brain tissue. The gene for glutamate
ammonia ligase was upregulated compared to control in the casein-based high BDE47diet, suggesting potential impacts on downstream
synaptic transmission. The study supported a previously observed regulation of Igfbp2 in brain with BDE47 exposure. Genes for hepatic metabolic enzymes were not influenced by BDE47. Potential neurotoxic effects
and neurobehavioural aberrations after perinatal exposure to high levels of BDE47 were not readily observed in mice pups with
the present experimental exposure regimes and methods of analysis. 相似文献