全文获取类型
收费全文 | 20315篇 |
免费 | 1651篇 |
国内免费 | 1735篇 |
出版年
2024年 | 52篇 |
2023年 | 261篇 |
2022年 | 520篇 |
2021年 | 1072篇 |
2020年 | 766篇 |
2019年 | 908篇 |
2018年 | 872篇 |
2017年 | 656篇 |
2016年 | 860篇 |
2015年 | 1293篇 |
2014年 | 1542篇 |
2013年 | 1597篇 |
2012年 | 1851篇 |
2011年 | 1701篇 |
2010年 | 984篇 |
2009年 | 936篇 |
2008年 | 1066篇 |
2007年 | 911篇 |
2006年 | 773篇 |
2005年 | 627篇 |
2004年 | 569篇 |
2003年 | 495篇 |
2002年 | 436篇 |
2001年 | 358篇 |
2000年 | 317篇 |
1999年 | 293篇 |
1998年 | 211篇 |
1997年 | 192篇 |
1996年 | 183篇 |
1995年 | 144篇 |
1994年 | 165篇 |
1993年 | 125篇 |
1992年 | 137篇 |
1991年 | 133篇 |
1990年 | 117篇 |
1989年 | 85篇 |
1988年 | 71篇 |
1987年 | 56篇 |
1986年 | 52篇 |
1985年 | 58篇 |
1984年 | 30篇 |
1983年 | 41篇 |
1982年 | 24篇 |
1981年 | 12篇 |
1980年 | 20篇 |
1979年 | 20篇 |
1978年 | 12篇 |
1977年 | 13篇 |
1975年 | 14篇 |
1974年 | 12篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
841.
Fan Zhang Haoting Chen Li Na Zhao Hui Liu Teresa M. Przytycka Jie Zheng 《BMC systems biology》2016,10(Z1):S7
Background
Cellular responses to extracellular perturbations require signaling pathways to capture and transmit the signals. However, the underlying molecular mechanisms of signal transduction are not yet fully understood, thus detailed and comprehensive models may not be available for all the signaling pathways. In particular, insufficient knowledge of parameters, which is a long-standing hindrance for quantitative kinetic modeling necessitates the use of parameter-free methods for modeling and simulation to capture dynamic properties of signaling pathways.Results
We present a computational model that is able to simulate the graded responses to degradations, the sigmoidal biological relationships between signaling molecules and the effects of scheduled perturbations to the cells. The simulation results are validated using experimental data of protein phosphorylation, demonstrating that the proposed model is capable of capturing the main trend of protein activities during the process of signal transduction. Compared with existing simulators, our model has better performance on predicting the state transitions of signaling networks.Conclusion
The proposed simulation tool provides a valuable resource for modeling cellular signaling pathways using a knowledge-based method.842.
Luqiao?Wang Hangfei?Fu Gayani?Nanayakkara Yafeng?Li Ying?Shao Candice?Johnson Jiali?Cheng William?Y.?Yang Fan?Yang Muriel?Lavallee Yanjie?Xu Xiaoshu?Cheng Hang?Xi Jonathan?Yi Jun?Yu Eric?T.?Choi Hong?Wang Xiaofeng?Yang
Background
Caspase-1 is present in the cytosol as an inactive zymogen and requires the protein complexes named “inflammasomes” for proteolytic activation. However, it remains unclear whether the proteolytic activity of caspase-1 is confined only to the cytosol where inflammasomes are assembled to convert inactive pro-caspase-1 to active caspase-1.Methods
We conducted meticulous data analysis method?s on proteomic, protein interaction, protein intracellular localization, and gene expressions of 114 experimentally identified caspase-1 substrates and 38 caspase-1 interaction proteins in normal physiological conditions and in various pathologies.Results
We made the following important findings: (1) Caspase-1 substrates and interaction proteins are localized in various intracellular organelles including nucleus and secreted extracellularly; (2) Caspase-1 may get activated in situ in the nucleus in response to intra-nuclear danger signals; (3) Caspase-1 cleaves its substrates in exocytotic secretory pathways including exosomes to propagate inflammation to neighboring and remote cells; (4) Most of caspase-1 substrates are upregulated in coronary artery disease regardless of their subcellular localization but the majority of metabolic diseases cause no significant expression changes in caspase-1 nuclear substrates; and (5) In coronary artery disease, majority of upregulated caspase-1 extracellular substrate-related pathways are involved in induction of inflammation; and in contrast, upregulated caspase-1 nuclear substrate-related pathways are more involved in regulating cell death and chromatin regulation.Conclusions
Our identification of novel caspase-1 trafficking sites, nuclear and extracellular inflammasomes, and extracellular caspase-1-based inflammation propagation model provides a list of targets for the future development of new therapeutics to treat cardiovascular diseases, inflammatory diseases, and inflammatory cancers.843.
844.
845.
846.
Ruoying Lu Li Ma Feng He Dong Yu Ruozhi Fan Yangming Zhang Zheping Long Xiaoyu Zhang Yang Yang 《Bioprocess and biosystems engineering》2016,39(3):381-390
The ability of the white-rot fungus Ganoderma sp.En3 to decolorize different kinds of dyes widely applied in the textile and dyeing industry, including the anthraquinone dye Remazol Brilliant Blue R (RBBR), indigo dye indigo carmine and triphenylmethane dye methyl green, was evaluated in this study. Ganoderma sp.En3 had a strong capability of decolorizing high concentrations of RBBR, indigo carmine and methyl green. Obvious reduction of Chemical Oxygen Demand was observed after decolorization of different dyes. Ganoderma sp.En3 had a strong ability to tolerate RBBR, indigo carmine and methyl green with high concentrations. High concentrations of RBBR, indigo carmine and methyl green could also be efficiently decolorized by the crude enzyme of Ganoderma sp.En3. Different redox mediators such as syringaldehyde, acetosyringone and acetovanillone could enhance the decolorization capability for higher concentration of indigo carmine and methyl green. Different metal ions had little effect on the ability of the crude enzyme to decolorize indigo carmine and methyl green. Our study suggested that Ganoderma sp.En3 had a strong capability for decolorizing and tolerating high concentrations of different types of dyes such as RBBR, indigo carmine and methyl green. 相似文献
847.
Jian-Dong Zhang Zhi-Mei Cui Xiao-Jun Fan Hua-Lei Wu Hong-Hong Chang 《Bioprocess and biosystems engineering》2016,39(4):603-611
Two uncharacterized nicotinamide adenine dinucleotide (NADH) oxidases (named as LpNox1, LpNox2) from Lactobacillus pentosus ATCC 8041 were cloned and overexpressed in Escherichia coli BL21 (DE3). The sequence analysis revealed that the two enzymes are water-forming Noxs with 64 % and 52 % identity to LbNox from Lactobacillus brevis DSM 20054. The optimal pH and temperature of the purified LpNox1 and LpNox2 were 7.0 and 8.0 and 35 and 40 °C, respectively, with K M of 99.0 μM (LpNox1) and 27.6 μM (LpNox2), and yielding catalytic efficiency k cat/K M of 1.0 and 0.2 μM?1 s?1, respectively. Heat inactivation studies revealed that the two enzymes are relatively instable. The application of LpNox1 for the regeneration of NAD+ was demonstrated by coupling with a glycerol dehydrogenase-catalyzed oxidation of glycerol to 1,3-dihydroxyacetone. The characteristics of the LpNox1 could prove to be of interest in industrial application such as NAD+ regeneration in dehydrogenase-catalyzed oxidations. 相似文献
848.
Liang Li Xiufeng Wang Liping Yang Yajun Fan Xiaojuan Zhu Xingzhi Wang 《Plant biotechnology reports》2016,10(4):207-217
Transient expression of foreign genes by Agrobacterium infiltration is a versatile technique that can be used as a rapid tool for functional protein production in plants. A reproducible protocol of large-scale production of foreign proteins via the novel plant transient expression system in Pisum sativum L. was established in our study. Non-detached plants from soil-independent culture were used as the target organ, and vacuum infiltrating mediated by Agrobacterium tumefaciens harboring green fluorescent protein (GFP) gene was performed. Step-by-step optimization was performed and showed that the quality of plant material as well as agro-infiltration conditions were the major factors influencing the gene expression. Monitoring the transient GFP expression daily, the highest expression level was achieved on the 8th day post-infiltration. Evidence of anti-acidic fibroblast growth factor-single chain variable fragment (anti-aFGF-scFv) gene expression in pea seedling was also achieved using agro-mediated vacuum infiltration system. Our work proves that the system is suitable for the largescale production of pharmaceutical proteins. The in planta infiltration system described here provides a powerful tool to explore easily gene expression in Pisum sativum L. avoiding tissue culture steps and the labor-intensive generation of transgenic plants. 相似文献
849.
Orou?G.?GaoueEmail authorView authors OrcID profile Jiang?Jiang Wandi?Ding Folashade?B.?Agusto Suzanne?Lenhart 《Theoretical Ecology》2016,9(3):287-297
Harvesting wild plants for non-timber forest products (NTFPs) can be ecologically sustainable–without long-term consequences to the dynamics of targeted and associated species–but it may not be economically satisfying because it fails to provide enough revenues for local people over time. In several cases, the same species can be harvested for NTFP and also logged for timber. Three decades of studies on the sustainability of NTFP harvest for local people’s livelihood have failed to successfully integrate these socio-economic and ecological factors. We apply optimal control theory to investigate optimal strategies for the combinations of non-lethal (e.g., NTFP) and lethal (e.g., timber) harvest that minimize the cost of harvesting while maximizing the benefits (revenue) that accrue to harvesters and the conservation value of harvested ecosystems. Optimal harvesting strategies include starting with non-lethal NTFP harvest and postponing lethal timber harvesting to begin after a few years. We clearly demonstrate that slow growth species have lower optimal harvesting rates, objective functional values and profits than fast growth species. However, contrary to expectation, the effect of species lifespan on optimal harvesting rates was weak suggesting that life history is a better indicator of species resilience to harvest than lifespan. Overall, lethal or nonlethal harvest rates must be <40 % to ensure optimality. This optimal rate is lower than commonly reported sustainable harvest rates for non-timber forest products. 相似文献
850.
Association between the change in body mass index from early adulthood to midlife and subsequent type 2 diabetes mellitus 下载免费PDF全文
Yiming Mu Chao Liu Jiajun Zhao Lulu Chen Qiang Li Tao Yang Li Yan Qin Wan Shengli Wu Yan Liu Guixia Wang Zuojie Luo Xulei Tang Gang Chen Yanan Huo Zhengnan Gao Qing Su Youmin Wang Guijun Qin Huacong Deng Xuefeng Yu Feixia Shen Li Chen Liebin Zhao Jichao Sun Lin Ding Yu Xu Min Xu Meng Dai Tiange Wang Di Zhang Jieli Lu Yufang Bi Shenghan Lai Donghui Li Weiqing Wang Guang Ning 《Obesity (Silver Spring, Md.)》2016,24(3):703-709