全文获取类型
收费全文 | 2149篇 |
免费 | 127篇 |
国内免费 | 149篇 |
专业分类
2425篇 |
出版年
2024年 | 3篇 |
2023年 | 31篇 |
2022年 | 66篇 |
2021年 | 136篇 |
2020年 | 80篇 |
2019年 | 80篇 |
2018年 | 80篇 |
2017年 | 49篇 |
2016年 | 89篇 |
2015年 | 127篇 |
2014年 | 165篇 |
2013年 | 174篇 |
2012年 | 212篇 |
2011年 | 171篇 |
2010年 | 90篇 |
2009年 | 77篇 |
2008年 | 101篇 |
2007年 | 103篇 |
2006年 | 94篇 |
2005年 | 80篇 |
2004年 | 41篇 |
2003年 | 50篇 |
2002年 | 46篇 |
2001年 | 19篇 |
2000年 | 32篇 |
1999年 | 32篇 |
1998年 | 23篇 |
1997年 | 15篇 |
1996年 | 15篇 |
1995年 | 17篇 |
1994年 | 13篇 |
1993年 | 13篇 |
1992年 | 19篇 |
1991年 | 14篇 |
1990年 | 9篇 |
1989年 | 11篇 |
1988年 | 8篇 |
1987年 | 7篇 |
1986年 | 8篇 |
1985年 | 3篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1982年 | 3篇 |
1981年 | 4篇 |
1980年 | 3篇 |
1979年 | 2篇 |
1974年 | 2篇 |
1971年 | 1篇 |
1966年 | 2篇 |
排序方式: 共有2425条查询结果,搜索用时 15 毫秒
71.
Xinyi Zhang Jinglei Nie Yuanmin Zheng Jie Ren An-Ping Zeng 《Biotechnology and bioengineering》2020,117(12):3677-3687
Protein lipoylation is essential for the function of many key enzymes but barely studied kinetically. Here, the two-step reaction cascade of H protein lipoylation catalyzed by the multifunctional enzyme lipoate–protein ligase A (LplA) was quantitatively and differentially studied. We discovered new phenomena and unusual kinetics of the cascade: (a) the speed of the first reaction is faster than the second one by two orders of magnitude, leading to high accumulation of the intermediate lipoyl-AMP (Lip-AMP); (b) Lip-AMP is hydrolyzed, but only significantly at the presence of H protein and in competition with the lipoylation; (c) both the lipoylation of H protein and its hydrolysis is enhanced by the apo and lipoylated forms of H protein and a mutant without the lipoylation site. A conceptual mechanistic model is proposed to explain these experimental observations in which conformational change of LplA upon interaction with H protein and competitive nucleophilic attacks play key roles. 相似文献
72.
Yu Chen Huang Nie Li Tian Li Tong Lujia Yang Ning Lao Hailong Dong Hanfei Sang Lize Xiong 《Neurochemical research》2013,38(2):364-370
Nicotine has been reported to exert certain protective effect in the Parkinson’s and Alzheimer’s diseases. Whether it has a similar action in focal cerebral ischemia was unclear. In the present study, rats received either an injection of (?)-nicotine hydrogen tartrate salt (1.2 mg/kg, i.p.) or the vehicle 2 h before the 120 min middle cerebral artery occlusion. Neurological deficits and histological injury were assessed at 24 h after reperfusion. The content of endocannabinoids and the expression of cannabinoid receptor CB1 in brain tissues were determined at different time points after nicotine administration. Results showed that nicotine administration ameliorated neurological deficits and reduced infarct volume induced by cerebral ischemia in the rats. The neuroprotective effect was partially reversed by CB1 blockage. The content of the endocannabinoids N-arachidonylethanolamine and 2-arachidonoylglycerol, as well as the expression of cannabinoid receptor CB1 were up-regulated in brain tissues after nicotine delivery. These results suggest that endogenous cannabinoid system is involved in the nicotine-induced neuroprotection against transient focal cerebral ischemia. 相似文献
73.
Huang Nie Zhengwu Peng Ning Lao Hailong Dong Lize Xiong 《Neurochemical research》2013,38(8):1758-1767
Sevoflurane anesthesia in infant rats can result in long-term cognitive impairment, possibly by inhibiting neurogenesis. The hippocampus is critical for memory consolidation and is one of only two mammalian brain regions where neural stem cells (NSCs) are renewed continuously throughout life. To elucidate the pathogenesis of sevoflurane-induced cognitive dysfunction, we measured the effects of clinical sevoflurane doses on the survival, proliferation, and differentiation of hippocampal NSCs. Neural stem cells were isolated from Sprague–Dawley rat embryos, expanded in vitro, and exposed to sevoflurane at 0.5, 1, or 1.5 minimal alveolar concentration (MAC) for 1 or 6 h. Two days after treatment, cell viability, cytotoxicity, and apoptosis rate were estimated by WST-1 assay, lactate dehydrogenase (LDH) activity, and TdT-mediated dUTP-biotin nick end labeling (TUNEL), respectively, while proliferation rate was assessed by 5-ethynyl-2′-deoxyuridine (BrdU) incorporation and Ki67 staining. Differentiation was assayed 7 days after treatment by immunocytochemistry and Western blots of neuron and glial markers. The phosphorylation level of p44/42 extracellular regulated kinases (ERK1/2) was measured in the proliferation and differentiation phases respectively. Sevoflurane at 1 MAC or 1.5 MAC for 1 h increased viable cell number whereas a 6 h exposure at these same concentrations suppressed proliferation and promoted apoptotic death (P < 0.01). Sevoflurane had no effect on NSC differentiation, and a sub-clinical concentration (0.5 MAC) altered neither proliferation nor viability. The phosphorylation level of ERK1/2 increased after 1 h of 1 MAC or 1.5 MAC of sevoflurane exposure in the proliferation phase, but not in the differentiation phase. Brief (1 h) exposure to sevoflurane at clinical concentrations enhanced proliferation of cultured NSCs possibly mediated by ERK1/2, but a 6 h exposure suppressed proliferation and induced apoptosis. Prolonged sevoflurane exposure may decrease the self-renewal capacity of hippocampal NSCs, resulting in cognitive deficits. 相似文献
74.
75.
76.
77.
Courtney A. Schultz Thomas D. Sisk Barry R. Noon Martin A. Nie 《The Journal of wildlife management》2013,77(3):428-444
In 2012, the United States Forest Service (USFS) promulgated new planning regulations in accordance with the National Forest Management Act (NFMA). These regulations represent the most significant change in federal forest policy in decades and have sweeping implications for wildlife populations. We provide a brief overview of the history of the NFMA planning regulations and their wildlife provisions and review the current science on planning for effective wildlife conservation at the landscape scale. We then discuss the approach to wildlife conservation planning in the 2012 rule and compare it to alternatives that were not selected and previous iterations of the planning rule. The new planning rule is of concern because of its highly discretionary nature and the inconsistency between its intent on the one hand and operational requirements on the other. Therefore, we recommend that the USFS include in the Directives for implementing the rule commitments to directly monitor populations of selected species of conservation concern and focal species and to maintain the viability of both categories of species. Additional guidance must be included to ensure the effective selection of species of conservation concern and focal species, and these categories should overlap when possible. If the USFS determines that the planning unit is not inherently capable of maintaining viable populations of a species, this finding should be made available for scientific review and public comment, and in such cases the USFS should commit to doing nothing that would further impair the viability of such species. In cases where extrinsic factors decrease the viability of species, the USFS has an increased, not lessened, responsibility to protect those species. Monitoring plans must include trigger points that will initiate a review of management actions, and plans must include provisions to ensure monitoring takes place as planned. If wildlife provisions in forest plans are implemented so that they are enforceable and ensure consistency between intent and operational requirements, this will help to prevent the need for additional listings under the Endangered Species Act and facilitate delisting. Although the discretionary nature of the wildlife provisions in the planning rule gives cause for concern, forward-thinking USFS officials have the opportunity under the 2012 rule to create a robust and effective framework for wildlife conservation planning. © 2013 The Wildlife Society. 相似文献
78.
Zhao Shan Qinglin Han Jia Nie Xuezhi Cao Zuojia Chen Shuying Yin Yayi Gao Fang Lin Xiaohui Zhou Ke Xu Huimin Fan Zhikang Qian Bing Sun Jin Zhong Bin Li Andy Tsun 《The Journal of biological chemistry》2013,288(49):35093-35103
Although lysine methylation is classically known to regulate histone function, its role in modulating antiviral restriction factor activity remains uncharacterized. Interferon-induced transmembrane protein 3 (IFITM3) was found monomethylated on its lysine 88 residue (IFITM3-K88me1) to reduce its antiviral activity, mediated by the lysine methyltransferase SET7. Vesicular stomatitis virus and influenza A virus infection increased IFITM3-K88me1 levels by promoting the interaction between IFITM3 and SET7, suggesting that this pathway could be hijacked to support infection; conversely, IFN-α reduced IFITM3-K88me1 levels. These findings may have important implications in the design of therapeutics targeting protein methylation against infectious diseases. 相似文献
79.
Weixi Zhang Ying Nie Lei Chong Xiaohong Cai Hui Zhang Beibei Lin Yafeng Liang Changchong Li 《Life sciences》2013,92(17-19):890-895
AimsIn the present study, we determined whether Phosphoinositide 3-kinase (PI3K) and Notch signal pathways are involved in the expression of cyclinD1, cyclinA and p27kip1 which were key molecules in controlling cell cycling from CD4+ T lymphocyte in animal model of asthma.Main methodsOvalbumin (OVA) sensitized murine model of asthma was used to investigate the expression of cyclin D1, cyclin A, and p27kip1 by splenic CD4+ T lymphocytes. We further observed the effect of specific inhibitor of PI3K(LY294002) and specific inhibitor of Notch(DAPT) on the proliferation of such CD4+ T lymphocytes.Key findingsWe found that the expression of cyclinD1 and cyclinA was upregulated at both protein and mRNA levels in asthma group while p27kip1 was down-regulated. Both LY294002 and DAPT inhibit the proliferation of CD4+ T lymphocytes in a time- and dose-dependent manner. Furthermore, LY294002 and DAPT have additive effect in down-regulation of cyclinD1 and upregulation of p27kip1. An upregulation of cyclinA, although not statistically significant, was also observed.SignificanceThese data suggested that PI3K signal pathway and Notch signal pathway may coordinately regulate the cell proliferation and differentiation processes through up-regulating cyclinD1 and down-regulating p27kip1 of CD4+ T lymphocytes. 相似文献
80.