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   1217篇
  免费   90篇
  2023年   6篇
  2022年   11篇
  2021年   21篇
  2020年   14篇
  2019年   22篇
  2018年   16篇
  2017年   24篇
  2016年   37篇
  2015年   54篇
  2014年   68篇
  2013年   89篇
  2012年   102篇
  2011年   90篇
  2010年   65篇
  2009年   70篇
  2008年   80篇
  2007年   95篇
  2006年   79篇
  2005年   76篇
  2004年   65篇
  2003年   58篇
  2002年   61篇
  2001年   12篇
  2000年   4篇
  1999年   8篇
  1998年   10篇
  1997年   5篇
  1996年   2篇
  1995年   6篇
  1994年   4篇
  1993年   5篇
  1992年   5篇
  1991年   3篇
  1990年   3篇
  1989年   4篇
  1988年   1篇
  1987年   2篇
  1986年   2篇
  1985年   3篇
  1984年   1篇
  1983年   3篇
  1981年   3篇
  1980年   5篇
  1979年   2篇
  1978年   2篇
  1977年   2篇
  1975年   1篇
  1971年   3篇
  1965年   1篇
  1964年   2篇
排序方式: 共有1307条查询结果,搜索用时 31 毫秒
11.
A structural component of mitotic chromosomes that partially explains the compaction of DNA within mitotic chromosomes is suggested on the basis of the occurrence of long, regular cylindrical structures in preparations of isolated human chromosomes. These structures, unit fibers, of a rather constant diameter of about 4,000 Å have been postulated to be formed by coiling of the 250T2–300 Å solenoid chromatin fiber that itself is formed by coiling of the 100 Å string of nucleosome fiber. The human chromatid would thus be composed by a hierarchy of helices with contraction ratios for DNA at each level of coiling of 7 (string of nucleosomes), 5 (solenoid) and 40 (4,000 Å unit fiber or super-solenoid) which results in an overall contraction ratio for DNA in the unit fiber structures of about 1,400, which is approximately 5-fold less than the final contraction of DNA in intact chromatids of condensed metaphase chromosomes. The present report concerns more detailed studies with respect to the dimensions and cytochemical properties of the unit fiber structures observed in preparations of isolated human mitotic chromosomes that provide direct and indirect evidence in support of their super-solenoid structure and relate to known properties of human mitotic chromosomes.  相似文献   
12.
The International Journal of Life Cycle Assessment - To estimate life cycle impacts from introducing the yield-enhancing inoculant containing the nitrogen-fixing bacterium Bradyrhizobium japonicum...  相似文献   
13.
Subsequent to their introduction in the 1950s, Arctic charr Salvelinus alpinus have been able to establish a self-sustaining population that has adapted to the unique conditions of the sub-Antarctic Kerguelen Islands. Here, 48 individuals (198–415 mm) were caught with gillnets and their basic biology and feeding ecology were examined using stable isotope analysis. The Lac des Fougères population split use of littoral and pelagic resources evenly, although larger fish relied more heavily on littoral production and appear to follow the size-dependent life history habitat template seen in many Scandinavian lakes where smaller sized individuals occupy the pelagic zone and larger individuals dominate the littoral habitat. In Kerguelen, Arctic charr mature at the same ages (5.6 years) as Arctic charr in both sub-Arctic and Arctic lakes. Although mortality was average in comparison to comparator sub-Arctic lakes, it was high in comparison to Arctic lakes. Maximal age (>7+) was at the lower end of the range typically seen in sub-Arctic lakes. Although they inhabit a resource-poor environment, Kerguelen Arctic charr showed no evidence of cannibalism. Thus, while Arctic charr can survive and reproduce in the relatively unproductive Kerguelen lake environments, survival and growth nevertheless appear to be traded off against survival and longevity. The uniqueness of the population location and the recency of its introduction suggest that further monitoring of the population has the potential to yield valuable insights into both the adaptability of the species and its likely responses to ongoing large-scale environmental change as represented by climate change.  相似文献   
14.
Seagrass ecosystems have suffered significant declines globally and focus is shifting to restoration efforts. A key component to successful restoration is an understanding of the genetic factors potentially influencing restoration success. This includes understanding levels of connectivity between restoration locations and neighboring seagrass populations that promote natural recovery (source and sink populations), the identification of potential donor populations, and assessment of genetic diversity of restored meadows and material used for restoration. In this study, we carry out genetic surveys of 352 individuals from 13 populations using 11 polymorphic microsatellite loci to inform seagrass restoration activities by: (1) understanding levels of genetic and genotypic diversity within meadows; and (2) understanding genetic structure and patterns of connectivity among these meadows to determine which source sites may be most appropriate to assist recovery of three restoration sites. The study identified high genotypic diversity within the locations analyzed from the Port of Gladstone and Rodd's Bay region, indicating sexual reproduction is important in maintaining populations. Overall, we detected significant genetic structuring among sites with the Bayesian structure analysis identifying genetic clusters that largely conformed to a northern, central, and southern region. This suggests limited gene flow between regions, although there does appear to be some connectivity within regions. The hydrodynamic models showed that seeds were largely locally retained, while fragments were more widely dispersed. Limited gene flow between regions suggests donor material for restoration should be sourced locally where possible.  相似文献   
15.
α‐Helical coiled coil structures, which are noncovalently associated heptad repeat peptide sequences, are ubiquitous in nature. Similar amphipathic repeat sequences have also been found in helix‐containing proteins and have played a central role in de novo design of proteins. In addition, they are promising tools for the construction of nanomaterials. Small‐angle X‐ray scattering (SAXS) has emerged as a new biophysical technique for elucidation of protein topology. Here, we describe a systematic study of the self‐assembly of a small ensemble of coiled coil sequences using SAXS and analytical ultracentrifugation (AUC), which was correlated with molecular dynamics simulations. Our results show that even minor sequence changes have an effect on the folding topology and the self‐assembly and that these differences can be observed by a combination of AUC, SAXS, and circular dichroism spectroscopy. A small difference in these methods was observed, as SAXS for one peptide and revealed the presence of a population of longer aggregates, which was not observed by AUC. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.  相似文献   
16.
17.
The pan‐eukaryotic endoplasmic reticulum (ER) membrane protein Arv1 has been suggested to play a role in intracellular sterol transport. We tested this proposal by comparing sterol traffic in wild‐type and Arv1‐deficient Saccharomyces cerevisiae. We used fluorescence microscopy to track the retrograde movement of exogenously supplied dehydroergosterol (DHE) from the plasma membrane (PM) to the ER and lipid droplets and high performance liquid chromatography to quantify, in parallel, the transport‐coupled formation of DHE esters. Metabolic labeling and subcellular fractionation were used to assay anterograde transport of ergosterol from the ER to the PM. We report that sterol transport between the ER and PM is unaffected by Arv1 deficiency. Instead, our results indicate differences in ER morphology and the organization of the PM lipid bilayer between wild‐type and arv1Δ cells suggesting a distinct role for Arv1 in membrane homeostasis. In arv1Δ cells, specific defects affecting single C‐terminal transmembrane domain proteins suggest that Arv1 might regulate membrane insertion of tail‐anchored proteins involved in membrane homoeostasis .  相似文献   
18.
Managing and controlling wildlife species within Europe is an acknowledged part of conservation management, yet deciding and setting a population target in order to control a population is perceived to be conceptually very challenging. We interviewed stakeholders, within a variety of governmental and non-governmental organizations, to evaluate their perspectives about setting population targets as part of waterbird management for controlling population sizes. We conclude that the setting of a quantifiable population target is beneficial as a measurable objective for monitoring and evaluating management actions. However, it must be recognised as just one possible measurable objective and there may well be multiple supporting objectives that encapsulate the management aims of different stakeholders. When considering wide-scale control of waterbirds species, where it is likely that population size matters, any population target should be coupled to the issues being addressed. We highlight that it is important to actively engage with stakeholders as part of the decision-making process, not only to gain consensus but to share knowledge. A clear understanding of the context and the rationale for controlling a waterbird species is needed to align the interests of diverse stakeholders. The provision of scientific data and the continuous monitoring of management actions is viewed as beneficial and demanded by stakeholders, as part of any decision-making process when setting population targets. This facilitates effective evaluation of management actions, helping managers make wise decisions as well as enabling the continued development of management plans.  相似文献   
19.
The proper identification of differentially methylated CpGs is central in most epigenetic studies. The Illumina HumanMethylation450 BeadChip is widely used to quantify DNA methylation; nevertheless, the design of an appropriate analysis pipeline faces severe challenges due to the convolution of biological and technical variability and the presence of a signal bias between Infinium I and II probe design types. Despite recent attempts to investigate how to analyze DNA methylation data with such an array design, it has not been possible to perform a comprehensive comparison between different bioinformatics pipelines due to the lack of appropriate data sets having both large sample size and sufficient number of technical replicates. Here we perform such a comparative analysis, targeting the problems of reducing the technical variability, eliminating the probe design bias and reducing the batch effect by exploiting two unpublished data sets, which included technical replicates and were profiled for DNA methylation either on peripheral blood, monocytes or muscle biopsies. We evaluated the performance of different analysis pipelines and demonstrated that: (1) it is critical to correct for the probe design type, since the amplitude of the measured methylation change depends on the underlying chemistry; (2) the effect of different normalization schemes is mixed, and the most effective method in our hands were quantile normalization and Beta Mixture Quantile dilation (BMIQ); (3) it is beneficial to correct for batch effects. In conclusion, our comparative analysis using a comprehensive data set suggests an efficient pipeline for proper identification of differentially methylated CpGs using the Illumina 450K arrays.  相似文献   
20.

Background

Socio-demographic factors and area of residence might influence the development of esophageal and gastric cancer. Large-scale population-based research can determine the role of such factors.

Methods

This population-based cohort study included all Swedish residents aged 30–84 years in 1990–2007. Educational level, marital status, place of birth, and place of residence were evaluated with regard to mortality from esophageal or gastric cancer. Cox regression yielded hazard ratios (HR) with 95% confidence intervals (CI), adjusted for potential confounding.

Results

Among 84 920 565 person-years, 5125 and 12 230 deaths occurred from esophageal cancer and gastric cancer, respectively. Higher educational level decreased the HR of esophageal cancer (HR = 0.61, 95%CI 0.42–0.90 in women, HR = 0.71, 95%CI 0.60–0.84 in men) and gastric cancer (HR = 0.80, 95%CI 0.63–1.03 in women, HR = 0.73, 95%CI 0.64–0.83 in men). Being unmarried increased HR of esophageal cancer (HR = 1.64, 95%CI 1.35–1.99 in women, HR = 1.64, 95%CI 1.50–1.80 in men), but not of gastric cancer. Being born in low density populated areas increased HR of gastric cancer (HR = 1.23, 95%CI 1.10–1.38 in women, HR = 1.37, 95%CI 1.25–1.50 in men), while no strong association was found with esophageal cancer. Living in densely populated areas increased HR of esophageal cancer (HR = 1.31, 95%CI 1.14–1.50 in women, HR = 1.40, 95%CI 1.29–1.51 in men), but not of gastric cancer.

Conclusion

These socio-demographic inequalities in cancer mortality warrant efforts to investigate possible preventable mechanisms and to promote and support healthier lifestyles among deprived groups.  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