全文获取类型
收费全文 | 5248篇 |
免费 | 391篇 |
国内免费 | 499篇 |
专业分类
6138篇 |
出版年
2024年 | 9篇 |
2023年 | 71篇 |
2022年 | 174篇 |
2021年 | 311篇 |
2020年 | 207篇 |
2019年 | 229篇 |
2018年 | 253篇 |
2017年 | 181篇 |
2016年 | 236篇 |
2015年 | 317篇 |
2014年 | 394篇 |
2013年 | 397篇 |
2012年 | 492篇 |
2011年 | 435篇 |
2010年 | 275篇 |
2009年 | 266篇 |
2008年 | 277篇 |
2007年 | 254篇 |
2006年 | 195篇 |
2005年 | 146篇 |
2004年 | 161篇 |
2003年 | 138篇 |
2002年 | 91篇 |
2001年 | 76篇 |
2000年 | 78篇 |
1999年 | 73篇 |
1998年 | 43篇 |
1997年 | 47篇 |
1996年 | 46篇 |
1995年 | 40篇 |
1994年 | 32篇 |
1993年 | 27篇 |
1992年 | 26篇 |
1991年 | 17篇 |
1990年 | 17篇 |
1989年 | 19篇 |
1988年 | 8篇 |
1987年 | 9篇 |
1986年 | 9篇 |
1985年 | 10篇 |
1984年 | 6篇 |
1983年 | 3篇 |
1979年 | 8篇 |
1975年 | 7篇 |
1974年 | 4篇 |
1971年 | 4篇 |
1970年 | 4篇 |
1969年 | 2篇 |
1966年 | 3篇 |
1965年 | 3篇 |
排序方式: 共有6138条查询结果,搜索用时 15 毫秒
151.
Asht Mangal Mishra Xiaoxiao Bai Basavaraju G. Sanganahalli Stephen G. Waxman Olena Shatillo Olli Grohn Fahmeed Hyder Asla Pitk?nen Hal Blumenfeld 《PloS one》2014,9(4)
Traumatic brain injury (TBI) contributes to about 10% of acquired epilepsy. Even though the mechanisms of post-traumatic epileptogenesis are poorly known, a disruption of neuronal networks predisposing to altered neuronal synchrony remains a viable candidate mechanism. We tested a hypothesis that resting state BOLD-fMRI functional connectivity can reveal network abnormalities in brain regions that are connected to the lesioned cortex, and that these changes associate with functional impairment, particularly epileptogenesis. TBI was induced using lateral fluid-percussion injury in seven adult male Sprague-Dawley rats followed by functional imaging at 9.4T 4 months later. As controls we used six sham-operated animals that underwent all surgical operations but were not injured. Electroencephalogram (EEG)-functional magnetic resonance imaging (fMRI) was performed to measure resting functional connectivity. A week after functional imaging, rats were implanted with bipolar skull electrodes. After recovery, rats underwent pentyleneterazol (PTZ) seizure-susceptibility test under EEG. For image analysis, four pairs of regions of interests were analyzed in each hemisphere: ipsilateral and contralateral frontal and parietal cortex, hippocampus, and thalamus. High-pass and low-pass filters were applied to functional imaging data. Group statistics comparing injured and sham-operated rats and correlations over time between each region were calculated. In the end, rats were perfused for histology. None of the rats had epileptiform discharges during functional imaging. PTZ-test, however revealed increased seizure susceptibility in injured rats as compared to controls. Group statistics revealed decreased connectivity between the ipsilateral and contralateral parietal cortex and between the parietal cortex and hippocampus on the side of injury as compared to sham-operated animals. Injured animals also had abnormal negative connectivity between the ipsilateral and contralateral parietal cortex and other regions. Our data provide the first evidence on abnormal functional connectivity after experimental TBI assessed with resting state BOLD-fMRI. 相似文献
152.
Jian-Bo Xie Zhenglin Du Lanqing Bai Changfu Tian Yunzhi Zhang Jiu-Yan Xie Tianshu Wang Xiaomeng Liu Xi Chen Qi Cheng Sanfeng Chen Jilun Li 《PLoS genetics》2014,10(3)
We provide here a comparative genome analysis of 31 strains within the genus Paenibacillus including 11 new genomic sequences of N2-fixing strains. The heterogeneity of the 31 genomes (15 N2-fixing and 16 non-N2-fixing Paenibacillus strains) was reflected in the large size of the shell genome, which makes up approximately 65.2% of the genes in pan genome. Large numbers of transposable elements might be related to the heterogeneity. We discovered that a minimal and compact nif cluster comprising nine genes nifB, nifH, nifD, nifK, nifE, nifN, nifX, hesA and nifV encoding Mo-nitrogenase is conserved in the 15 N2-fixing strains. The nif cluster is under control of a σ70-depedent promoter and possesses a GlnR/TnrA-binding site in the promoter. Suf system encoding [Fe–S] cluster is highly conserved in N2-fixing and non-N2-fixing strains. Furthermore, we demonstrate that the nif cluster enabled Escherichia coli JM109 to fix nitrogen. Phylogeny of the concatenated NifHDK sequences indicates that Paenibacillus and Frankia are sister groups. Phylogeny of the concatenated 275 single-copy core genes suggests that the ancestral Paenibacillus did not fix nitrogen. The N2-fixing Paenibacillus strains were generated by acquiring the nif cluster via horizontal gene transfer (HGT) from a source related to Frankia. During the history of evolution, the nif cluster was lost, producing some non-N2-fixing strains, and vnf encoding V-nitrogenase or anf encoding Fe-nitrogenase was acquired, causing further diversification of some strains. In addition, some N2-fixing strains have additional nif and nif-like genes which may result from gene duplications. The evolution of nitrogen fixation in Paenibacillus involves a mix of gain, loss, HGT and duplication of nif/anf/vnf genes. This study not only reveals the organization and distribution of nitrogen fixation genes in Paenibacillus, but also provides insight into the complex evolutionary history of nitrogen fixation. 相似文献
153.
154.
155.
S. W. Englander L. Mayne Y. Bai T. R. Sosnick 《Protein science : a publication of the Protein Society》1997,6(5):1101-1109
This discussion, prepared for the Protein Society's symposium honoring the 100th anniversary of Kaj Linderstrøm-Lang, shows how hydrogen exchange approaches initially conceived and implemented by Lang and his colleagues some 50 years ago are contributing to current progress in structural biology. Examples are chosen from the active protein folding field. Hydrogen exchange methods now make it possible to define the structure of protein folding intermediates in various contexts: as tenuous molten globule forms at equilibrium under destabilizing conditions, in kinetic intermediates that exist for less than one second, and as infinitesimally populated excited state forms under native conditions. More generally, similar methods now find broad application in studies of protein structure, energetics, and interactions. This article considers the rise of these capabilities from their inception at the Carlsberg Labs to their contemporary role as a significant tool of modern structural biology. 相似文献
156.
157.
Taoyan Liu Siyao Zhang Chenwu Huang Shuhong Ma Rui Bai Yanan Li Yun Chang Chenwen Hang Amina Saleem Tao Dong Tianwei Guo Youxu Jiang Wenjing Lu Lina Zhang Luo Jianwen Hongfeng Jiang Feng Lan 《Journal of cellular and molecular medicine》2021,25(7):3469-3483
The use of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is limited in drug discovery and cardiac disease mechanism studies due to cell immaturity. Micro-scaled grooves can promote the maturation of cardiomyocytes by aligning them in order, but the mechanism of cardiomyocytes alignment has not been studied. From the level of calcium activity, gene expression and cell morphology, we verified that the W20H5 grooves can effectively promote the maturation of cardiomyocytes. The transient receptor potential channels (TRP channels) also play an important role in the maturation and development of cardiomyocytes. These findings support the engineered hPSC-CMs as a powerful model to study cardiac disease mechanism and partly mimic the myocardial morphological development. The important role of the TRP channels in the maturation and development of myocardium is first revealed. 相似文献
158.
Luo B Parker GJ Cooksey RC Soesanto Y Evans M Jones D McClain DA 《The Journal of biological chemistry》2007,282(10):7172-7180
The hexosamine biosynthesis pathway (HBP) serves as a nutrient sensor and has been implicated in the development of type 2 diabetes. We previously demonstrated that fatty acid oxidation was enhanced in transgenic mouse adipocytes, wherein the rate-limiting enzyme of the HBP, glutamine:fructose-6-phosphate amidotransferase (GFA), was overexpressed. To explore the molecular mechanism of the HBP-induced fatty acid oxidation in adipocytes, we studied AMP-activated protein kinase (AMPK), an energy sensor that stimulates fatty acid oxidation by regulating acetyl-CoA carboxylase (ACC) activity. Phosphorylation and activity of AMPK were increased in transgenic fat pads and in 3T3L1 adipocytes treated with glucosamine to stimulate hexosamine flux. Glucosamine also stimulated phosphorylation of ACC and fatty acid oxidation in 3T3L1 adipocytes, and these stimulatory effects were diminished by adenovirus-mediated expression of a dominant negative AMPK in 3T3L1 adipocytes. Conversely, blocking the HBP with a GFA inhibitor reduced AMPK activity, ACC phosphorylation, and fatty acid oxidation. These changes are not explained by alterations in the cellular AMP/ATP ratio. Further demonstrating that AMPK is regulated by the HBP, we found that AMPK was recognized by succinylated wheat germ agglutinin, which specifically binds O-GlcNAc. The levels of AMPK in succinylated wheat germ agglutinin precipitates correlated with hexosamine flux in mouse fat pads and 3T3L1 adipocytes. Moreover, removal of O-GlcNAc by hexosaminidase reduced AMPK activity. We conclude that chronically high hexosamine flux stimulates fatty acid oxidation by activating AMPK in adipocytes, in part through O-linked glycosylation. 相似文献
159.
【目的】针对人胰腺α-淀粉酶这个糖代谢途径中重要的靶蛋白,建立α-淀粉酶抑制剂高通量筛选模型。【方法】采用毕赤酵母表达系统克隆和表达人胰腺α-淀粉酶;利用酶的催化特性建立α-淀粉酶抑制剂筛选模型;应用该模型对放线菌发酵液冻干物进行高通量筛选;通过构建16S rRNA系统发育树分析阳性菌株的分类地位。【结果】成功克隆、表达了具催化活性的人胰腺α-淀粉酶;建立了α-淀粉酶抑制剂的筛选模型;对近2000株放线菌的发酵液冻干物进行高通量筛选,最终得到14株α-淀粉酶抑制剂产生菌株,且在分类学上具有丰富的菌种多样性。【结论】本研究建立的α-淀粉酶抑制剂高通量筛选模型具有很强的实用价值,可用于新型淀粉酶抑制剂类降糖药物的开发。 相似文献
160.
Liu Xinrong Liu Shuya Tang Yong Pu Zhengjia Xiao Hong Gao Jieying Yin Qi Jia Yan Bai Qunhua 《Neurochemical research》2021,46(6):1514-1539
Neurochemical Research - Gut microbial dysbiosis and alteration of gut microbiota composition in Parkinson's disease (PD) have been increasingly reported, no recognized therapies are available... 相似文献