首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   9628篇
  免费   466篇
  国内免费   457篇
  2023年   84篇
  2022年   113篇
  2021年   150篇
  2020年   159篇
  2019年   263篇
  2018年   352篇
  2017年   308篇
  2016年   184篇
  2015年   171篇
  2014年   365篇
  2013年   380篇
  2012年   279篇
  2011年   284篇
  2010年   209篇
  2009年   234篇
  2008年   314篇
  2007年   297篇
  2006年   251篇
  2005年   230篇
  2004年   171篇
  2003年   161篇
  2002年   132篇
  2001年   99篇
  2000年   101篇
  1999年   80篇
  1998年   80篇
  1997年   82篇
  1996年   73篇
  1995年   67篇
  1994年   80篇
  1993年   62篇
  1992年   43篇
  1991年   49篇
  1990年   56篇
  1989年   39篇
  1988年   39篇
  1986年   38篇
  1985年   497篇
  1984年   598篇
  1983年   329篇
  1982年   521篇
  1981年   392篇
  1980年   413篇
  1979年   337篇
  1978年   290篇
  1977年   238篇
  1976年   221篇
  1975年   222篇
  1974年   203篇
  1973年   154篇
排序方式: 共有10000条查询结果,搜索用时 406 毫秒
991.
Climate change is a major threat to global biodiversity, and its impacts can act synergistically to heighten the severity of other threats. Most research on projecting species range shifts under climate change has not been translated to informing priority management strategies on the ground. We develop a prioritization framework to assess strategies for managing threats to biodiversity under climate change and apply it to the management of invasive animal species across one‐sixth of the Australian continent, the Lake Eyre Basin. We collected information from key stakeholders and experts on the impacts of invasive animals on 148 of the region's most threatened species and 11 potential strategies. Assisted by models of current distributions of threatened species and their projected distributions, experts estimated the cost, feasibility, and potential benefits of each strategy for improving the persistence of threatened species with and without climate change. We discover that the relative cost‐effectiveness of invasive animal control strategies is robust to climate change, with the management of feral pigs being the highest priority for conserving threatened species overall. Complementary sets of strategies to protect as many threatened species as possible under limited budgets change when climate change is considered, with additional strategies required to avoid impending extinctions from the region. Overall, we find that the ranking of strategies by cost‐effectiveness was relatively unaffected by including climate change into decision‐making, even though the benefits of the strategies were lower. Future climate conditions and impacts on range shifts become most important to consider when designing comprehensive management plans for the control of invasive animals under limited budgets to maximize the number of threatened species that can be protected.  相似文献   
992.
Tethering factors regulate the targeting of membrane‐enclosed vesicles under the control of Rab GTPases. p115, a golgin family tether, has been shown to participate in multiple stages of ER/Golgi transport. Despite extensive study, the mechanism of action of p115 is poorly understood. SNARE proteins make up the machinery for membrane fusion, and strong evidence shows that function of p115 is directly linked to its interaction with SNAREs. Using a gel filtration binding assay, we have demonstrated that in solution p115 stably interacts with ER/Golgi SNAREs rbet1 and sec22b, but not membrin and syntaxin 5. These binding preferences stemmed from selectivity of p115 for monomeric SNARE motifs as opposed to SNARE oligomers. Soluble monomeric rbet1 can compete off p115 from coat protein II (COPII) vesicles. Furthermore, excess p115 inhibits p115 function in trafficking. We conclude that monomeric SNAREs are a major binding site for p115 on COPII vesicles, and that p115 dissociates from its SNARE partners upon SNAREpin assembly. Our results suggest a model in which p115 forms a mixed p115/SNARE helix bundle with a monomeric SNARE, facilitates the binding activity and/or concentration of the SNARE at prefusion sites and is subsequently ejected as SNARE complex formation and fusion proceed.   相似文献   
993.
Systemic acquired resistance (SAR) is a plant defence response that provides immunity to distant uninfected leaves after an initial localised infection. The lipid transfer protein (LTP) Defective in Induced Resistance1 (DIR1) is an essential component of SAR that moves from induced to distant leaves following a SAR‐inducing local infection. To understand how DIR1 is transported to distant leaves during SAR, we analysed DIR1 movement in transgenic Arabidopsis lines with reduced cell‐to‐cell movement caused by the overexpression of Plasmodesmata‐Located Proteins PDLP1 and PDLP5. These PDLP‐overexpressing lines were defective for SAR, and DIR1 antibody signals were not observed in phloem sap‐enriched petiole exudates collected from distant leaves. Our data support the idea that cell‐to‐cell movement of DIR1 through plasmodesmata is important during long‐distance SAR signalling in Arabidopsis.  相似文献   
994.
995.

Background

The study of nuclear architecture using Chromosome Conformation Capture (3C) technologies is a novel frontier in biology. With further reduction in sequencing costs, the potential of Hi-C in describing nuclear architecture as a phenotype is only about to unfold. To use Hi-C for phenotypic comparisons among different cell types, conditions, or genetic backgrounds, Hi-C data processing needs to be more accessible to biologists.

Results

HiCdat provides a simple graphical user interface for data pre-processing and a collection of higher-level data analysis tools implemented in R. Data pre-processing also supports a wide range of additional data types required for in-depth analysis of the Hi-C data (e.g. RNA-Seq, ChIP-Seq, and BS-Seq).

Conclusions

HiCdat is easy-to-use and provides solutions starting from aligned reads up to in-depth analyses. Importantly, HiCdat is focussed on the analysis of larger structural features of chromosomes, their correlation to genomic and epigenomic features, and on comparative studies. It uses simple input and output formats and can therefore easily be integrated into existing workflows or combined with alternative tools.

Electronic supplementary material

The online version of this article (doi:10.1186/s12859-015-0678-x) contains supplementary material, which is available to authorized users.  相似文献   
996.
How health care providers are paid affects how medicine is practiced. It is thus important to assess provider payment models not only from the economic perspective but also from the ethical perspective. China recently started to reform the provider payment model in the health care system from fee‐for‐service to case‐based payment. This paper aims to examine this transition from an ethical perspective. We collected empirical studies on the impact of case‐based payment in the Chinese health care system and applied a systematic ethical matrix that integrates clinical ethics and public health ethics to analyze the empirical findings. We identified eleven prominent ethical issues related to case‐based payment. Some ethical problems of case‐based payment in China are comparable to ethical problems of managed care and diagnosis related groups in high‐income countries. However, in this paper we discuss in greater detail four specific ethical issues in the Chinese context: professionalism, the patient‐physician relationship, access to care and patient autonomy. Based on the analysis, we cautiously infer that case‐based payment is currently more ethically acceptable than fee‐for‐service in the context of China, mainly because it seems to lower financial barriers to access care. Nonetheless, it will be difficult to justify the implementation of case‐based payment if no additional measures are taken to monitor and minimize its existing negative ethical implications.  相似文献   
997.
The main goal of this research was to investigate how different factors influence membrane fouling. The impact of the different concentrations of activated sludge and the amount of extracellular polymer substances (EPS) were monitored. Two pilot plants with submerged membrane modules (hollow fiber and flat sheet) were operated and the raw wastewater was used.Humic substances were identified as the major components of EPS in the activated sludge (more than 34%) in both pilot plants. As the basic constituent in permeate, humic substances were identified as the most dominant components in the effluent (61%) in both pilot plants. Conversely, proteins were mostly analyzed in permeate and supernatant below the detection limit. The total amount of EPS [mg g−1 (VSS)] was similar for concentrations of activated sludge 6, 10 and 14 g L−1. Carbohydrates were identified as the component of EPS which tends most to clog membranes.  相似文献   
998.
999.
Activation of 5′-AMP-activated protein kinase (AMPK) is believed to be the mechanism by which the pharmaceuticals, metformin and phenformin, exert their beneficial effects for treatment of type 2 diabetes. These biguanide drugs elevate 5′-AMP, which allosterically activates AMPK and promotes phosphorylation on Thr172 of AMPK catalytic α subunits. Although kinases phosphorylating this site have been identified, phosphatases that dephosphorylate it are unknown. The aim of this study is to identify protein phosphatase(s) that dephosphorylate AMPKα-Thr172 within cells. Our initial data indicated that members of the protein phosphatase ce:sup>/ce:sup>/Mn2+-dependent (PPM) family and not those of the PPP family of protein serine/threonine phosphatases may be directly or indirectly inhibited by phenformin. Using antibodies raised to individual Ppm phosphatases that facilitated the assessment of their activities, phenformin stimulation of cells was found to decrease the ce:sup>/ce:sup>/Mn2+-dependent protein serine/threonine phosphatase activity of Ppm1E and Ppm1F, but not that attributable to other PPM family members, including Ppm1A/PP2Cα. Depletion of Ppm1E, but not Ppm1A, using lentiviral-mediated stable gene silencing, increased AMPKα-Thr172 phosphorylation approximately three fold in HEK293 cells. In addition, incubation of cells with low concentrations of phenformin and depletion of Ppm1E increased AMPK phosphorylation synergistically. Ppm1E and the closely related Ppm1F interact weakly with AMPK and assays with lysates of cells stably depleted of Ppm1F suggests that this phosphatase contributes to dephosphorylation of AMPK. The data indicate that Ppm1E and probably PpM1F are in cellulo AMPK phosphatases and that Ppm1E is a potential anti-diabetic drug target.  相似文献   
1000.
In barley, the eukaryotic translation initiation factor 4E (eIF4E) gene situated on chromosome 3H is recognized as an important source of resistance to the bymoviruses Barley yellow mosaic virus and Barley mild mosaic virus. In modern barley cultivars, two recessive eIF4E alleles, rym4 and rym5, confer different isolate-specific resistances. In this study, the sequence of eIF4E was analysed in 1090 barley landraces and noncurrent cultivars originating from 84 countries. An exceptionally high nucleotide diversity was evident in the coding sequence of eIF4E but not in either the adjacent MCT-1 gene or the sequence-related eIF(iso)4E gene situated on chromosome 1H. Surprisingly, all nucleotide polymorphisms detected in the coding sequence of eIF4E resulted in amino acid changes. A total of 47 eIF4E haplotypes were identified, and phylogenetic analysis using maximum likelihood provided evidence of strong positive selection acting on this barley gene. The majority of eIF4E haplotypes were found to be specific to distinct geographic regions. Furthermore, the eI4FE haplotype diversity (uh) was found to be considerably higher in East Asia, whereas SNP genotyping identified a comparatively low degree of genome-wide genetic diversity in 16 of 17 tested accessions (each carrying a different eIF4E haplotype) from this same region. In addition, selection statistic calculations using coalescent simulations showed evidence of non-neutral variation for eIF4E in several geographic regions, including East Asia, the region with a long history of the bymovirus-induced yellow mosaic disease. Together these findings suggest that eIF4E may play a role in barley adaptation to local habitats.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号