全文获取类型
收费全文 | 855篇 |
免费 | 66篇 |
国内免费 | 39篇 |
专业分类
960篇 |
出版年
2024年 | 4篇 |
2023年 | 10篇 |
2022年 | 20篇 |
2021年 | 43篇 |
2020年 | 26篇 |
2019年 | 34篇 |
2018年 | 28篇 |
2017年 | 23篇 |
2016年 | 38篇 |
2015年 | 58篇 |
2014年 | 52篇 |
2013年 | 63篇 |
2012年 | 59篇 |
2011年 | 62篇 |
2010年 | 18篇 |
2009年 | 30篇 |
2008年 | 38篇 |
2007年 | 27篇 |
2006年 | 37篇 |
2005年 | 24篇 |
2004年 | 17篇 |
2003年 | 26篇 |
2002年 | 24篇 |
2001年 | 21篇 |
2000年 | 20篇 |
1999年 | 19篇 |
1998年 | 11篇 |
1997年 | 17篇 |
1996年 | 10篇 |
1995年 | 5篇 |
1994年 | 5篇 |
1993年 | 3篇 |
1992年 | 5篇 |
1991年 | 6篇 |
1990年 | 4篇 |
1989年 | 5篇 |
1988年 | 7篇 |
1987年 | 6篇 |
1986年 | 5篇 |
1985年 | 3篇 |
1982年 | 3篇 |
1980年 | 3篇 |
1976年 | 3篇 |
1975年 | 6篇 |
1974年 | 3篇 |
1973年 | 4篇 |
1972年 | 4篇 |
1971年 | 6篇 |
1970年 | 3篇 |
1968年 | 2篇 |
排序方式: 共有960条查询结果,搜索用时 15 毫秒
11.
12.
Phenological sensitivity to climate change is higher in resident than in migrant bird populations among European cavity breeders 下载免费PDF全文
Jelmer M. Samplonius Lenka Bartošová Malcolm D. Burgess Andrey V. Bushuev Tapio Eeva Elena V. Ivankina Anvar B. Kerimov Indrikis Krams Toni Laaksonen Marko Mägi Raivo Mänd Jaime Potti János Török Miroslav Trnka Marcel E. Visser Herwig Zang Christiaan Both 《Global Change Biology》2018,24(8):3780-3790
Many organisms adjust their reproductive phenology in response to climate change, but phenological sensitivity to temperature may vary between species. For example, resident and migratory birds have vastly different annual cycles, which can cause differential temperature sensitivity at the breeding grounds, and may affect competitive dynamics. Currently, however, adjustment to climate change in resident and migratory birds have been studied separately or at relatively small geographical scales with varying time series durations and methodologies. Here, we studied differential effects of temperature on resident and migratory birds using the mean egg laying initiation dates from 10 European nest box schemes between 1991 and 2015 that had data on at least one resident tit species and at least one migratory flycatcher species. We found that both tits and flycatchers advanced laying in response to spring warming, but resident tit populations advanced more strongly in relation to temperature increases than migratory flycatchers. These different temperature responses have already led to a divergence in laying dates between tits and flycatchers of on average 0.94 days per decade over the current study period. Interestingly, this divergence was stronger at lower latitudes where the interval between tit and flycatcher phenology is smaller and winter conditions can be considered more favorable for resident birds. This could indicate that phenological adjustment to climate change by flycatchers is increasingly hampered by competition with resident species. Indeed, we found that tit laying date had an additional effect on flycatcher laying date after controlling for temperature, and this effect was strongest in areas with the shortest interval between both species groups. Combined, our results suggest that the differential effect of climate change on species groups with overlapping breeding ecology affects the phenological interval between them, potentially affecting interspecific interactions. 相似文献
13.
【目的】通过增加北京棒杆菌(Corynebacterium pekinense)PD-67芳香族氨基酸合成的前体物质磷酸烯醇式丙酮酸(PEP)的供应,解除终产物对芳香族氨基酸合成途径中第一个酶同时也是关键酶3-脱氧-D-阿拉伯庚酮糖-7-磷酸合酶(DS)的反馈抑制并提高抗反馈抑制的DS的活力,使碳流更多地流向芳香族氨基酸合成途径,从而积累更多L-色氨酸。【方法】运用PCR技术扩增北京棒杆菌PD-67磷酸烯醇式丙酮酸合酶基因pps,与表达载体连接构建重组质粒pXPS;运用重叠PCR技术定点突变大肠杆菌(Escherichia coli)受苯丙氨酸调控的DS基因aroG,使相应的编码氨基酸序列发生突变:Leu175Asp,新的基因命名为aroGfbr,与表达载体连接构建重组质粒pXA;构建pps和aroGfbr的共表达重组质粒pXAPS。将3个重组质粒分别转入菌株PD-67,构建工程菌株PD-67/pXPS、PD-67/pXA和PD-67/pXAPS。通过摇瓶发酵研究工程菌株的发酵特性。【结果】酶活分析结果表明,pps基因和aroGfbr基因在北京棒杆菌PD-67中均实现了表达。工程菌株PD-67/pXA粗酶液DS抗反馈抑制分析表明,AroGfbr已解除酪氨酸和苯丙氨酸的反馈抑制。过表达pps基因和aroGfbr基因分别使工程菌L-色氨酸产量提高12.1%和26.8%,双基因共表达可使工程菌的产酸量提高35.9%。【结论】北京棒杆菌PD-67pps基因的过表达以及大肠杆菌来源的解除反馈抑制的aroGfbr的过表达均有助于增加PD-67 L-色氨酸的合成,而双基因的共表达可以进一步提高L-色氨酸的积累量。 相似文献
14.
AMPKα1‐LDH pathway regulates muscle stem cell self‐renewal by controlling metabolic homeostasis 下载免费PDF全文
Marine Theret Gaëtan Juban Sabrina Ben Larbi Michèle Weiss‐Gayet Laurent Bultot Marc Foretz Dominique Desplanches Pascual Sanz Zizhao Zang Lin Yang Guillaume Vial Benoit Viollet Kei Sakamoto Anne Brunet Bénédicte Chazaud Rémi Mounier 《The EMBO journal》2017,36(13):1946-1962
Control of stem cell fate to either enter terminal differentiation versus returning to quiescence (self‐renewal) is crucial for tissue repair. Here, we showed that AMP‐activated protein kinase (AMPK), the master metabolic regulator of the cell, controls muscle stem cell (MuSC) self‐renewal. AMPKα1?/? MuSCs displayed a high self‐renewal rate, which impairs muscle regeneration. AMPKα1?/? MuSCs showed a Warburg‐like switch of their metabolism to higher glycolysis. We identified lactate dehydrogenase (LDH) as a new functional target of AMPKα1. LDH, which is a non‐limiting enzyme of glycolysis in differentiated cells, was tightly regulated in stem cells. In functional experiments, LDH overexpression phenocopied AMPKα1?/? phenotype, that is shifted MuSC metabolism toward glycolysis triggering their return to quiescence, while inhibition of LDH activity rescued AMPKα1?/? MuSC self‐renewal. Finally, providing specific nutrients (galactose/glucose) to MuSCs directly controlled their fate through the AMPKα1/LDH pathway, emphasizing the importance of metabolism in stem cell fate. 相似文献
15.
16.
Bing Chen Ting Xu Changle Zhou Luoyu Wang Ning Yang Ze Wang Hao-Ming Dong Zhi Yang Yu-Feng Zang Xi-Nian Zuo Xu-Chu Weng 《PloS one》2015,10(12)
Individual differences in mind and behavior are believed to reflect the functional variability of the human brain. Due to the lack of a large-scale longitudinal dataset, the full landscape of variability within and between individual functional connectomes is largely unknown. We collected 300 resting-state functional magnetic resonance imaging (rfMRI) datasets from 30 healthy participants who were scanned every three days for one month. With these data, both intra- and inter-individual variability of six common rfMRI metrics, as well as their test-retest reliability, were estimated across multiple spatial scales. Global metrics were more dynamic than local regional metrics. Cognitive components involving working memory, inhibition, attention, language and related neural networks exhibited high intra-individual variability. In contrast, inter-individual variability demonstrated a more complex picture across the multiple scales of metrics. Limbic, default, frontoparietal and visual networks and their related cognitive components were more differentiable than somatomotor and attention networks across the participants. Analyzing both intra- and inter-individual variability revealed a set of high-resolution maps on test-retest reliability of the multi-scale connectomic metrics. These findings represent the first collection of individual differences in multi-scale and multi-metric characterization of the human functional connectomes in-vivo, serving as normal references for the field to guide the use of common functional metrics in rfMRI-based applications. 相似文献
17.
Zang M Gong J Luo L Zhou J Xiang X Huang W Huang Q Luo X Olbrot M Peng Y Chen C Luo Z 《The Journal of biological chemistry》2008,283(46):31429-31437
Raf kinases are essential for regulating cell proliferation, survival, and tumorigenesis. However, the mechanisms by which Raf is activated are still incompletely understood. Phosphorylation plays a critical role in Raf activation in response to mitogens. The present study characterizes phosphorylation of Ser338, a crucial event for Raf-1 activation. Here we report that mutation of Lys375 to Met diminishes phosphorylation of Ser338 on both wild type Raf-1 in cells treated with epidermal growth factor (EGF) or 12-O-tetradecanoylphorbol-13-acetate (TPA) and a constitutively active mutant in which Tyr340/Tyr341 are replaced by 2 aspartic acids, a conserved substitution present in natural B-Raf. The loss of Ser338 phosphorylation in these Raf mutants is not engendered by a mutation-induced conformational change, inasmuch as mutation of another site (Ser471 to Ala) in the activation segment also abolishes Ser338 phosphorylation, whereas both the kinase-dead mutants of Raf-1 are phosphorylated well by active Pak1. Furthermore, our data demonstrate that EGF-stimulated phosphorylation of Ser338 is inhibited by Sorafenib, a Raf kinase inhibitor, but not by the MEK inhibitor U0126. Interestingly, a kinase-dead mutation and Sorafenib also markedly reduce phosphorylation of Ser445 on B-Raf, a site equivalent to Raf-1 Ser338. Finally, our data reveal that Ser338 is phosphorylated on inactive Raf-1 by an active mutant of Raf-1 when they are dimerized in cells and that artificial dimerization of Raf-1 causes Ser338 phosphorylation, accompanied by activation of ERK1/2. Altogether, our data suggest that Ser338 on Raf-1 is autophosphorylated in response to mitogens. 相似文献
18.
Liangjie Xu Tianxin Geng Guangyao Zang Li Bo Yi Liang Hong Zhou Jinchuan Yan 《Journal of cellular and molecular medicine》2020,24(8):4659-4667
The role of exosomes derived from endothelial cells (ECs) in the progression of atherosclerosis (AS) and inflammation remains largely unexplored. We aimed to investigate whether exosome derived from CD137‐modified ECs (CD137‐Exo) played a major role in AS and to elucidate the potential mechanism underlying the inflammatory effect. Exosomes derived from mouse brain microvascular ECs treated with agonist anti‐CD137 antibody were used to explore the effect of CD137 signalling in AS and inflammation in vitro and vivo. CD137‐Exo efficiently induced the progression of AS in ApoE?/? mice. CD137‐Exo increased the proportion of Th17 cells both in vitro and vivo. The IL‐6 contained in CD137‐Exo which is regulated by Akt and NF‐КB pathway was verified to activate Th17 cell differentiation. IL‐17 increased apoptosis, inhibited cell viability and improved lactate dehydrogenase (LDH) release in ECs subjected to inflammation induced by lipopolysaccharide (LPS). The expression of soluble intercellular adhesion molecule1 (sICAM‐1), monocyte chemoattractant protein‐1 (MCP‐1) and E‐selectin in the supernatants of ECs after IL‐17 treatment was dramatically increased. CD137‐Exo promoted the progression of AS and Th17 cell differentiation via NF‐КB pathway mediated IL‐6 expression. This finding provided a potential method to prevent local and peripheral inflammation in AS. 相似文献
19.
20.
Du Xuemei Fang Ting Liu Yan Huang Liying Wang Xiaoli Zhang Jie Cui Yangbo Zang Maosen Wang Guoying Fu Junjie Liu Yunjun 《In vitro cellular & developmental biology. Plant》2020,56(2):159-168
In Vitro Cellular & Developmental Biology - Plant - Callus induction in plants is similar to pluripotent stem cell induction in animals and can incite global changes in gene expression.... 相似文献