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   1690篇
  免费   168篇
  国内免费   35篇
  2024年   6篇
  2023年   40篇
  2022年   41篇
  2021年   39篇
  2020年   96篇
  2019年   122篇
  2018年   83篇
  2017年   63篇
  2016年   77篇
  2015年   69篇
  2014年   56篇
  2013年   139篇
  2012年   69篇
  2011年   80篇
  2010年   69篇
  2009年   82篇
  2008年   80篇
  2007年   98篇
  2006年   69篇
  2005年   53篇
  2004年   49篇
  2003年   46篇
  2002年   37篇
  2001年   45篇
  2000年   27篇
  1999年   24篇
  1998年   15篇
  1997年   21篇
  1996年   28篇
  1995年   17篇
  1994年   14篇
  1993年   12篇
  1992年   11篇
  1991年   10篇
  1990年   18篇
  1989年   6篇
  1988年   6篇
  1987年   7篇
  1986年   13篇
  1985年   8篇
  1984年   7篇
  1983年   4篇
  1982年   6篇
  1981年   4篇
  1980年   4篇
  1979年   4篇
  1978年   3篇
  1975年   4篇
  1974年   5篇
  1973年   2篇
排序方式: 共有1893条查询结果,搜索用时 15 毫秒
71.
African swine fever virus(ASFV), as a member of the large DNA viruses, may regulate autophagy and apoptosis by inhibiting programmed cell death. However, the function of ASFV proteins has not been fully elucidated, especially the role of autophagy in ASFV infection. One of three Pyrroline-5-carboxylate reductases(PYCR), is primarily involved in conversion of glutamate to proline. Previous studies have shown that depletion of PYCR2 was related to the induction of autophagy. In the present study, we found for the first time that ASFV E199 L protein induced a complete autophagy process in Vero and HEK-293 T cells. Through co-immunoprecipitation coupled with mass spectrometry(CoIP-MS)analysis, we firstly identified that E199 L interact with PYCR2 in vitro. Importantly, our work provides evidence that E199 L down-regulated the expression of PYCR2, resulting in autophagy activation. Overall, our results demonstrate that ASFV E199 L protein induces complete autophagy through interaction with PYCR2 and down-regulate the expression level of PYCR2, which provide a valuable reference for the role of autophagy during ASFV infection and contribute to the functional clues of PYCR2.  相似文献   
72.
我国高度重视野生动物保护事业, 认真履行野生动物保护国际义务, 积极鼓励公众参与, 以扩大野生动物保护事业的公众基础。已有文献多关注了公众的国内野生动物保护意愿, 鲜有文献关注公众对国际野生动物的保护意愿, 难以为促进公众参与国际野生动物保护事业提供决策参考。本研究以全球旗舰物种非洲象(Loxodonta africana)为例, 结合非洲象保护的相关研究与实践, 构建拓展的计划行为理论框架, 通过线下和线上调研获取数据, 运用结构方程模型, 从态度、规范、知觉行为控制、过去经验及个体特征五个方面, 分析了我国公众的非洲象保护意愿及影响因素。结果表明: (1) 68.5%的公众具有非洲象保护愿意; (2)公众规范(系数为0.422)、过去经验(系数为0.253)、知觉行为控制(系数为0.160)、保护态度(系数为0.156)对保护意愿存在显著的正向影响; 男性公众(系数为-0.054)的保护意愿低于女性公众; 居住在西部地区的公众(系数为0.066)保护意愿更高; (3)模型整体通过了拟合检验, 表明研究结果具有稳健性。本研究的政策建议如下: (1)明确政策导向作用, 提升公众的道德义务感和社会责任感; (2)加强宣传教育, 丰富公众知识经验, 培育公众积极的保护态度; (3)拓宽保护参与渠道, 提高公众知觉行为控制; (4)制定合理方案, 提升保护宣教等实践活动成效。  相似文献   
73.
Human and animal African trypanosomoses, or sleeping sickness and Nagana, are neglected vector-borne parasitic diseases caused by protozoa belonging to the Trypanosoma genus. Advances in proteomics offer new tools to better understand host–vector–parasite crosstalks occurring during the complex parasitic developmental cycle, and to determine the outcome of both transmission and infection. In this review, we summarize proteomics studies performed on African trypanosomes and on the interactions with their vector and mammalian hosts. We discuss the contributions and pitfalls of using diverse proteomics tools, and argue about the interest of pathogenoproteomics, both to generate advances in basic research on the best knowledge and understanding of host–vector–pathogen interactions, and to lead to the concrete development of new tools to improve diagnosis and treatment management of trypanosomoses in the near future.  相似文献   
74.
This case study of the Estonian Genome Project (EGP) analyses the Estonian policy decision to construct a national human gene bank. Drawing upon qualitative data from newspaper articles and public policy documents, it focuses on how proponents use discourse to link the EGP to the broader political goal of securing Estonia's position within the Western/European scientific and cultural space. This dominant narrative is then situated within the analytical notion of the “brand state”, which raises potentially negative political consequences for this type of market‐driven genomic research. Considered against the increasing number of countries engaging in gene bank and/or gene database projects, this analysis of Estonia elucidates issues that cross national boundaries, while also illuminating factors specific to this small, post‐Soviet state as it enters the global biocybernetic economy.  相似文献   
75.
The study's objective is to survey the attitudes of Chinese people living in Hong Kong toward genomic science and technology (GST) and their ethical and social implications. Using a 24-item questionnaire, 877 Cantonese-speaking residents between age 18 and 64 with minimum high school education are interviewed by telephone. Multiple regression analysis identifies education level as the most important demographic variable. Overall, respondents have mild agreement with genetic determinism and the use of GST for disease prevention but not for non-therapeutic genetic enhancement and production of “genetically modified” crops or meat. Respondents strongly believe that GST tampers with nature and resources should be used to solve other healthcare problems first. Respondents also show little concern that personal genetic information may be abused by their employers or schools and have only a minimal willingness to share personal genetic information with their family members.  相似文献   
76.
Summary

The rapid bioassessment method, SASS (South African Scoring System) has been developed to assess water quality in riverine ecosystems. It is a scoring system based on the presence or absence of macroinvertebrate groups, and yields three values, namely SASS4 Score, Number of Taxa and Average Score Per Taxon (ASPT). The current and future use of SASS, including incorporation into the National Biomonitoring Programme for Riverine Ecosystems, necessitates evaluation of this bioassessment method. This study focuses on three aspects. namely spatial variation in SASS scores, including regional and longitudinal (sub-regional) variation; temporal variation in SASS scores, and the effect of biotope availability on SASS scores.  相似文献   
77.
CpG Island Methylator Phenotype (CIMP) is one of the underlying mechanisms in colorectal cancer (CRC). This study aimed to define a methylome signature in CRC through a methylation microarray analysis and a compilation of promising CIMP markers from the literature. Illumina HumanMethylation27 (IHM27) array data was generated and analyzed based on statistical differences in methylation data (1st approach) or based on overall differences in methylation percentages using lower 95% CI (2nd approach). Pyrosequencing was performed for the validation of nine genes. A meta-analysis was used to identify CIMP and non-CIMP markers that were hypermethylated in CRC but did not yet make it to the CIMP genes’ list. Our 1st approach for array data analysis demonstrated the limitations in selecting genes for further validation, highlighting the need for the 2nd bioinformatics approach to adequately select genes with differential aberrant methylation. A more comprehensive list, which included non-CIMP genes, such as APC, EVL, CD109, PTEN, TWIST1, DCC, PTPRD, SFRP1, ICAM5, RASSF1A, EYA4, 30ST2, LAMA1, KCNQ5, ADHEF1, and TFPI2, was established. Array data are useful to categorize and cluster colonic lesions based on their global methylation profiles; however, its usefulness in identifying robust methylation markers is limited and rely on the data analysis method. We have identified 16 non-CIMP-panel genes for which we provide rationale for inclusion in a more comprehensive characterization of CIMP+ CRCs. The identification of a definitive list for methylome specific genes in CRC will contribute to better clinical management of CRC patients.  相似文献   
78.
《Epigenetics》2013,8(4):503-512
The identification of genes that are differentially methylated in colorectal cancer (CRC) has potential value for both diagnostic and therapeutic interventions specifically in high-risk populations such as African Americans (AAs). However, DNA methylation patterns in CRC, especially in AAs, have not been systematically explored and remain poorly understood. Here, we performed DNA methylome profiling to identify the methylation status of CpG islands within candidate genes involved in critical pathways important in the initiation and development of CRC. We used reduced representation bisulfite sequencing (RRBS) in colorectal cancer and adenoma tissues that were compared with DNA methylome from a healthy AA subject’s colon tissue and peripheral blood DNA. The identified methylation markers were validated in fresh frozen CRC tissues and corresponding normal tissues from AA patients diagnosed with CRC at Howard University Hospital. We identified and validated the methylation status of 355 CpG sites located within 16 gene promoter regions associated with CpG islands. Fifty CpG sites located within CpG islands—in genes ATXN7L1 (2), BMP3 (7), EID3 (15), GAS7 (1), GPR75 (24), and TNFAIP2 (1)—were significantly hypermethylated in tumor vs. normal tissues (P < 0.05). The methylation status of BMP3, EID3, GAS7, and GPR75 was confirmed in an independent, validation cohort. Ingenuity pathway analysis mapped three of these markers (GAS7, BMP3 and GPR) in the insulin and TGF-β1 network—the two key pathways in CRC. In addition to hypermethylated genes, our analysis also revealed that LINE-1 repeat elements were progressively hypomethylated in the normal-adenoma-cancer sequence. We conclude that DNA methylome profiling based on RRBS is an effective method for screening aberrantly methylated genes in CRC. While previous studies focused on the limited identification of hypermethylated genes, ours is the first study to systematically and comprehensively identify novel hypermethylated genes, as well as hypomethylated LINE-1 sequences, which may serve as potential biomarkers for CRC in African Americans. Our discovered biomarkers were intimately linked to the insulin/TGF-B1 pathway, further strengthening the association of diabetic disorders with colon oncogenic transformation.  相似文献   
79.
Little is known about the role of folate and polymorphisms associated with folate metabolism on prostate cancer risk in populations of African origin. We examined the relationship between serum folate and prostate cancer and whether any association was modified by genetic polymorphisms for folate metabolism. The study was case–control in design and consisted of 218 men 40–80 years old with newly diagnosed, histologically confirmed prostate cancer and 236 cancer-free men attending the same urology clinics in Jamaica, March 2005–July 2007. Serum folate was measured by an immunoassay method and genomic DNA evaluated for MTHR (C677T and A1298C), MTRR A66G, and MTR A2756G polymorphisms. Mean serum folate concentration was higher among cases (12.3 ± 4.1 nmol/L) than controls (9.7 ± 4.2 nmol/L). Serum folate concentration showed a positive association with prostate cancer (OR, 4.41; CI, 2.52–7.72 per 10 nmol/L) regardless of grade. No interactions were observed between genotype and folate concentration, but a weak gene effect was observed for MTHFR A1298C and low-grade prostate cancer. Larger studies to investigate the role of gene–gene/gene–diet interactions in Black men are needed.  相似文献   
80.
Climate models project a hot and dry future for Southern Africa. In this research, Maximum Entropy was used to model the extent to which climate change, land cover and distance from water edges may influence current and future distribution of the African skimmer in the mid-Zambezi Valley. Global Biodiversity Information Facility data collected between the years 2000–2019 were used to develop the models. Three models were built: one for current distribution and two for future distribution under Representative Concentration Pathways (RCPs) 2.6 and 6.0. Results revealed that annual precipitation and distance from water edges were the most important predictors of habitat suitability for the African skimmer under current and future climate. Temperature and land cover were least important in explaining current and future distribution of the species. The RCP 2.6 predicted future decrease in suitable habitat for the African skimmer in the mid-Zambezi Valley, while RCP 6.0 predicted future increase in suitable habitat for the species. This research conclusively revealed that precipitation and distance from water edges were consistently key predictors of suitable habitat for the African skimmer.  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