全文获取类型
收费全文 | 30342篇 |
免费 | 2382篇 |
国内免费 | 2071篇 |
专业分类
34795篇 |
出版年
2024年 | 67篇 |
2023年 | 440篇 |
2022年 | 1017篇 |
2021年 | 1703篇 |
2020年 | 1038篇 |
2019年 | 1341篇 |
2018年 | 1279篇 |
2017年 | 929篇 |
2016年 | 1271篇 |
2015年 | 1855篇 |
2014年 | 2208篇 |
2013年 | 2473篇 |
2012年 | 2766篇 |
2011年 | 2458篇 |
2010年 | 1480篇 |
2009年 | 1276篇 |
2008年 | 1504篇 |
2007年 | 1312篇 |
2006年 | 1152篇 |
2005年 | 941篇 |
2004年 | 791篇 |
2003年 | 664篇 |
2002年 | 594篇 |
2001年 | 535篇 |
2000年 | 470篇 |
1999年 | 483篇 |
1998年 | 269篇 |
1997年 | 290篇 |
1996年 | 292篇 |
1995年 | 282篇 |
1994年 | 253篇 |
1993年 | 179篇 |
1992年 | 276篇 |
1991年 | 185篇 |
1990年 | 151篇 |
1989年 | 151篇 |
1988年 | 92篇 |
1987年 | 85篇 |
1986年 | 60篇 |
1985年 | 68篇 |
1984年 | 29篇 |
1983年 | 32篇 |
1982年 | 18篇 |
1981年 | 15篇 |
1980年 | 12篇 |
1979年 | 9篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
992.
Yue-Qiang Wang Yong Yuan Zhen Yu Gui-Qin Yang Shun-Gui Zhou 《Current microbiology》2013,67(6):718-724
A Gram-positive, facultative anaerobic, motile, endospore-forming rod strain, designated DX-4T, was isolated from an electrochemically active biofilm. Growth occurred at 30–65 °C (optimum 55 °C), at pH 6.0–8.5 (optimum pH 7.0–7.5) and with <6 % (w/v) NaCl. Cells were catalase- and oxidase-positive. The main respiratory quinone was MK-7, the predominant polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol mannoside, and unidentified aminophospholipid, the DNA G+C content was 38.6 mol% and the major fatty acids (>5 %) were iso-C15:0 (38.9 %), iso-C17:0 (30.5 %), iso-C16:0 (5.6 %), and anteiso-C17:0 (5.2 %). The phylogenetic analysis based on 16S rRNA gene sequence comparisons revealed that strain DX-4T is a member of the genus Bacillus. The results of phenotypic, chemotaxonomic, and genotypic analyses clearly indicated that strain DX-4T represents a novel species, for which the name Bacillus borbori sp. nov. is proposed. The type strain is DX-4T (= CCTCC AB2012196T = KCTC 33103T). 相似文献
993.
Jian-Guo Hu Xing-Jun Wu Yi-Fan Feng Gang-ming Xi Ling-Xiao Deng Zhen-Huan Wang Rui Wang Lin Shen Jian-Sheng Zhou He-Zuo Lü 《Neurochemical research》2013,38(3):601-609
The conditioned medium from B104 neuroblastoma cells (B104CM) induces proliferation of oligodendrocyte progenitor cells (OPCs) in vitro. However, the molecular events that occur during B104CM-induced proliferation of OPCs has not been well clarified. In the present study, using OPCs immunopanned from embryonic day 14 Sprague–Dawley rat spinal cords, we explored the activation of several signaling pathways and the expression of several important immediate early genes (IEGs) and cyclins in OPCs in response to B104CM. We found that B104CM can induce OPC proliferation through the activation of the extracellular signal-regulated kinases 1 and 2 (Erk1/2), but not PI3K or p38 MAPK signaling pathways in vitro. The IEGs involved in B104CM-induced OPC proliferation include c-fos, c-jun and Id2, but not c-myc, fyn, or p21. The cyclins D1, D2 and E are also involved in B104CM-stimulated proliferation of OPCs. The activation of Erk results in subsequent expression of IEGs (such as c-fos, c-jun and Id-2) and cyclins (including cyclin D1, D2 and E), which play key roles in cell cycle initiation and OPC proliferation. Collectively, these results suggest that the phosphorylation of Erk1/2 is an important molecular event during OPC proliferation induced by B104CM. 相似文献
994.
Yi Huang Jianqing Zhou Huadan Ye Limin Xu Yanping Le Xi Yang Weifeng Xu Xiaoyan Huang Jiangfang Lian Shiwei Duan 《Gene》2013
The goal of our study is to evaluate the contribution of CXCL12 rs1746048 (hg19, chr10:44775574) to the risk of CHD in Han Chinese, and to summarize its role in CHD through meta-analysis of existing studies among various ethnic groups. Significant association is observed between rs1746048-C and an increased risk of CHD in Han Chinese (χ2 = 5.41, df = 1, P = 0.02). Post hoc analysis reveals an even stronger association of rs1746048 with the risk of CHD for subjects aged 65 years or older (genotype: χ2 = 8.39, df = 2, P = 0.015; allele: χ2 = 9.13, df = 1, P = 0.003, odd ratio (OR) = 1.91, 95% confidential interval (CI) = 1.25–2.91). A break down analysis by gender shows that rs1746048 is likely a CHD risk factor under the recessive model in males (CC + CT versus TT: P = 0.05, χ2 = 3.59, df = 1, OR = 1.72, 95% CI = 1.00–3.04). In addition, a meta-analysis of ten studies among over 107,000 individuals confirms that rs1746048 is a risk factor of CHD (P < 0.0001, OR = 1.12, 95% CI = 1.09–1.15) and this agrees with the findings of our case–control study in Han Chinese. 相似文献
995.
In DNA microarray studies, gene-set analysis (GSA) has become the focus of gene expression data analysis. GSA utilizes the gene expression profiles of functionally related gene sets in Gene Ontology (GO) categories or priori-defined biological classes to assess the significance of gene sets associated with clinical outcomes or phenotypes. Many statistical approaches have been proposed to determine whether such functionally related gene sets express differentially (enrichment and/or deletion) in variations of phenotypes. However, little attention has been given to the discriminatory power of gene sets and classification of patients. 相似文献
996.
Liang Guo Jia-Xin Huang Yuan Liu Xi Li Shui-Rong Zhou Shu-Wen Qian Yang Liu Hao Zhu Hai-Yan Huang Yong-Jun Dang Qi-Qun Tang 《Molecular and cellular biology》2013,33(16):3180-3190
Autophagy is a highly conserved self-digestion pathway involved in various physiological and pathophysiological processes. Recent studies have implicated a pivotal role of autophagy in adipocyte differentiation, but the molecular mechanism for its role and how it is regulated during this process are not clear. Here, we show that CCAAT /enhancer-binding protein β (C/EBPβ), an important adipogenic factor, is required for the activation of autophagy during 3T3-L1 adipocyte differentiation. An autophagy-related gene, Atg4b, is identified as a de novo target gene of C/EBPβ and is shown to play an important role in 3T3-L1 adipocyte differentiation. Furthermore, autophagy is required for the degradation of Klf2 and Klf3, two negative regulators of adipocyte differentiation, which is mediated by the adaptor protein p62/SQSTM1. Importantly, the regulation of autophagy by C/EBPβ and the role of autophagy in Klf2/3 degradation and in adipogenesis are further confirmed in mouse models. Our data describe a novel function of C/EBPβ in regulating autophagy and reveal the mechanism of autophagy during adipocyte differentiation. These new insights into the molecular mechanism of adipose tissue development provide a functional pathway with therapeutic potential against obesity and its related metabolic disorders. 相似文献
997.
998.
Jianhua Cao Jiao Yang Youhua Wang Jian Xu Zhengming Zhou Chun Cheng Xiaojuan Liu Xinghai Cheng Long Long Xingxing Gu 《Cellular and molecular neurobiology》2013,33(2):213-221
As a novel cell cycle protein, Spy1 enhances cell proliferation, promotes the G1/S transition as well as inhibits apoptosis in response to UV irradiation. Spy1 levels are tightly regulated during mammary development, and overexpression of Spy1 accelerates tumorigenesis in vivo. But little is known about the role of Spy1 in the pathological process of damage and regeneration of the peripheral nervous system. Here we established a rat sciatic nerve crush (SNC) model to examine the spatiotemporal expression of Spy1. Spy1 expression was elevated gradually after sciatic nerve crush and peaked at day 3. The alteration was due to the increased expression of Spy1 in axons and Schwann cells after SNC. Spy1 expression correlated closely with Schwann cells proliferation in sciatic nerve post injury. Furthermore, Spy1 largely localized in axons in the crushed segment, but rarely co-localized with GAP43. These findings suggested that Spy1 participated in the pathological process response to sciatic nerve injury and may be associated with Schwann cells proliferation and axons regeneration. 相似文献
999.
Fan Guo Huiwen Wang Liya Li Heng Zhou Haidong Wei Weilin Jin Qiang Wang Lize Xiong 《Cellular and molecular neurobiology》2013,33(3):443-452
This study aimed to investigate the protective effect of the M9 region (residues 290–562) of amino-Nogo-A fused to the human immunodeficiency virus trans-activator TAT in an in vitro model of ischemia–reperfusion induced by oxygen–glucose deprivation (OGD) in HT22 hippocampal neurons, and to investigate the role of NADPH oxidase in this protection. Transduction of TAT-M9 was analyzed by immunofluorescence staining and western blot. The biologic activity of TAT-M9 was assessed by its effects against OGD-induced HT22 cell damage, compared with a mutant M9 fusion protein or vehicle. Cellular viability and lactate dehydrogenase (LDH) release were assessed. Neuronal apoptosis was evaluated by flow cytometry. The Bax/Bcl-2 ratio was determined by western blotting. Reactive oxygen species (ROS) levels and NADPH oxidase activity were also measured in the presence or absence of an inhibitor or activator of NADPH oxidase. Our results confirmed the delivery of the protein into HT22 cells by immunofluorescence and western blot. Addition of 0.4 μmol/L TAT-M9 to the culture medium effectively improved neuronal cell viability and reduced LDH release induced by OGD. The fusion protein also protected HT22 cells from apoptosis, suppressed overexpression of Bax, and inhibited the reduction in Bcl-2 expression. Furthermore, TAT-M9, as well as apocynin, decreased NADPH oxidase activity and ROS content. The protective effects of the TAT-M9 were reversed by TBCA, an agonist of NADPH oxidase. In conclusion, TAT-M9 could be successfully transduced into HT22 cells, and protected HT22 cells against OGD damage by inhibiting NADPH oxidase-mediated oxidative stress. These findings suggest that the TAT-M9 protein may be an efficient therapeutic agent for neuroprotection. 相似文献
1000.
Qiulin Wu Lixia Gou Shuangjun Lin Jingdan Liang Jun Yin Xiufen Zhou Linquan Bai Derong An Zixin Deng Zhijun Wang 《Biochimie》2013
Calcimycin is a rare divalent cation specific ionophore antibiotic that has many biochemical and pharmaceutical applications. We have recently cloned and sequenced the Streptomyces chartreusis calcimycin biosynthesis gene cluster as well as identified the genes required for the synthesis of the polyketide backbone of calcimycin. Additional modifying or decorating enzymes are required to convert the polyketide backbone into the biologically active calcimycin. Using targeted mutagenesis of Streptomyces we were able to show that calM from the calcimycin biosynthesis gene cluster is required for calcimycin production. Inactivating calM by PCR targeting, caused high level accumulation of N-demethyl calcimycin. CalM in the presence of S-adenosyl-L-methionine converted N-demethyl calcimycin to calcimycin in vitro. The enzyme was determined to have a kinetic parameter of Km 276 μM, kcat 1.26 min−1 and kcat/Km 76.2 M−1 s−1. These results proved that CalM is a N-methyltransferase that is required for calcimycin biosynthesis, and they set the stage for generating much desired novel calcimycin derivatives by rational genetic and chemical engineering. 相似文献