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   2890篇
  免费   344篇
  国内免费   1篇
  2022年   30篇
  2021年   54篇
  2020年   51篇
  2019年   55篇
  2018年   80篇
  2017年   63篇
  2016年   108篇
  2015年   134篇
  2014年   165篇
  2013年   162篇
  2012年   198篇
  2011年   167篇
  2010年   147篇
  2009年   112篇
  2008年   135篇
  2007年   165篇
  2006年   141篇
  2005年   132篇
  2004年   141篇
  2003年   116篇
  2002年   113篇
  2001年   48篇
  2000年   50篇
  1999年   49篇
  1998年   38篇
  1997年   34篇
  1996年   24篇
  1995年   26篇
  1994年   31篇
  1993年   41篇
  1992年   45篇
  1991年   37篇
  1990年   36篇
  1989年   23篇
  1988年   27篇
  1987年   16篇
  1986年   27篇
  1985年   15篇
  1984年   16篇
  1983年   22篇
  1982年   22篇
  1981年   15篇
  1980年   16篇
  1979年   14篇
  1978年   12篇
  1977年   8篇
  1975年   10篇
  1974年   10篇
  1972年   10篇
  1971年   7篇
排序方式: 共有3235条查询结果,搜索用时 656 毫秒
101.
102.
Sulfate reduction is an appropriate approach for the treatment of effluents with sulfate and dissolved metals. In sulfate‐reducing reactors, acetate may largely contribute to the residual organic matter, because not all sulfate reducers are able to couple the oxidation of acetate to the reduction of sulfate, limiting the treatment efficiency. In this study, we investigated the diversity of a bacterial community in the biofilm of a laboratory scale down‐flow fluidized bed reactor, which was developed under sulfidogenic conditions at an influent pH between 4 and 6. The sequence analysis of the microbial community showed that the 16S rRNA gene sequence of almost 50% of the clones had a high similarity with Anaerolineaceae. At second place, 33% of the 16S rRNA phylotypes were affiliated with the sulfate‐reducing bacteria Desulfobacca acetoxidans and Desulfatirhabdium butyrativorans, suggesting that acetotrophic sulfate reduction was occurring in the system. The remaining bacterial phylotypes were related to fermenting bacteria found at the advanced stage of reactor operation. The results indicate that the acetotrophic sulfate‐reducing bacteria were able to remain within the biofilm, which is a significant result because few natural consortia harbor complete oxidizing sulfate‐reducers, improving the acetate removal via sulfate reduction in the reactor.  相似文献   
103.
Once hunted to the brink of extinction, humpback whales (Megaptera novaeangliae) in the North Atlantic have recently been increasing in numbers. However, uncertain information on past abundance makes it difficult to assess the extent of the recovery in this species. While estimates of pre-exploitation abundance based upon catch data suggest the population might be approaching pre-whaling numbers, estimates based on mtDNA genetic diversity suggest they are still only a fraction of their past abundance levels. The difference between the two estimates could be accounted for by inaccuracies in the catch record, by uncertainties surrounding the genetic estimate, or by differences in the timescale to which the two estimates apply. Here we report an estimate of long-term population size based on nuclear gene diversity. We increase the reliability of our genetic estimate by increasing the number of loci, incorporating uncertainty in each parameter and increasing sampling across the geographic range. We report an estimate of long-term population size in the North Atlantic humpback of ~112,000 individuals (95 % CI 45,000–235,000). This value is 2–3 fold higher than estimates based upon catch data. This persistent difference between estimates parallels difficulties encountered by population models in explaining the historical crash of North Atlantic humpback whales. The remaining discrepancy between genetic and catch-record values, and the failure of population models, highlights a need for continued evaluation of whale population growth and shifts over time, and continued caution about changing the conservation status of this population.  相似文献   
104.
The dengue envelope glycoprotein (E) is the major component of virion surface and its ectodomain is composed of domains I, II and III. This protein is the main target for the development of a dengue vaccine with induction of neutralizing antibodies. In the present work, we tested two different vaccination strategies, with combined immunizations in a prime/booster regimen or simultaneous inoculation with a DNA vaccine (pE1D2) and a chimeric yellow fever/dengue 2 virus (YF17D-D2). The pE1D2 DNA vaccine encodes the ectodomain of the envelope DENV2 protein fused to t-PA signal peptide, while the YF17D-D2 was constructed by replacing the prM and E genes from the 17D yellow fever vaccine virus by those from DENV2. Balb/c mice were inoculated with these two vaccines by different prime/booster or simultaneous immunization protocols and most of them induced a synergistic effect on the elicited immune response, mainly in neutralizing antibody production. Furthermore, combined immunization remarkably increased protection against a lethal dose of DENV2, when compared to each vaccine administered alone. Results also revealed that immunization with the DNA vaccine, regardless of the combination with the chimeric virus, induced a robust cell immune response, with production of IFN-γ by CD8+ T lymphocytes.  相似文献   
105.
The accumulation of β-amyloid peptides in the brain has been recognized as an essential factor in Alzheimer’s disease pathology. Several proteases, including Neprilysin (NEP), endothelin converting enzyme (ECE), and insulin degrading enzyme (IDE), have been shown to cleave β-amyloid peptides (Aβ). We have previously reported reductions in amyloid in APP+PS1 mice with increased expression of ECE. In this study we compared the vector-induced increased expression of NEP and IDE. We used recombinant adeno-associated viral vectors expressing either native forms of NEP (NEP-n) or IDE (IDE-n), or engineered secreted forms of NEP (NEP-s) or IDE (IDE-s). In a six-week study, immunohistochemistry staining for total Aβ was significantly decreased in animals receiving the NEP-n and NEP-s but not for IDE-n or IDE-s in either the hippocampus or cortex. Congo red staining followed a similar trend revealing significant decreases in the hippocampus and the cortex for NEP-n and NEP-s treatment groups. Our results indicate that while rAAV-IDE does not have the same therapeutic potential as rAAV-NEP, rAAV-NEP-s and NEP-n are effective at reducing amyloid loads, and both of these vectors continue to have significant effects nine months post-injection. As such, they may be considered reasonable candidates for gene therapy trials in AD.  相似文献   
106.
107.
Aberrant activation of MAP kinase signaling pathway and loss of tumor suppressor LKB1 have been implicated in lung cancer development and progression. Although oncogenic KRAS mutations are frequent, BRAF mutations (BRAFV600E) are found in 3% of human non-small cell lung cancers. Contrary to KRAS mutant tumors, BRAFV600E-induced tumors are benign adenomas that fail to progess. Interestingly, loss of tumor supressor LKB1 coexists with KRAS oncogenic mutations and synergizes in tumor formation and progression, however, its cooperation with BRAFV600E oncogene is unknown. Our results describe a lung cell population in neonates mice where expression of BRAFV600E leads to lung adenoma development. Importantly, expression of BRAFV600E concomitant with the loss of only a single-copy of Lkb1, overcomes senencence–like features of BRAFV600E-mutant adenomas leading malignization to carcinomas. These results posit LKB1 haploinsufficiency as a risk factor for tumor progression of BRAFV600E mutated lung adenomas in human cancer patients.  相似文献   
108.
Increasing evidences highlight the importance of DEAD-box RNA helicases in plant development and stress responses. In a previous study, we characterized the tomato res mutant (restored cell structure by salinity), showing chlorosis and development alterations that reverted under salt-stress conditions. Map-based cloning demonstrates that RES gene encodes SlDEAD39, a chloroplast-targeted DEAD-box RNA helicase. Constitutive expression of SlDEAD39 complements the res mutation, while the silencing lines had a similar phenotype than res mutant, which is also reverted under salinity. Functional analysis of res mutant proved SlDEAD39 is involved in the in vivo processing of the chloroplast, 23S rRNA, at the hidden break-B site, a feature also supported by in vitro binding experiments of the protein. In addition, our results show that other genes coding for chloroplast-targeted DEAD-box proteins are induced by salt-stress, which might explain the rescue of the res mutant phenotype. Interestingly, salinity restored the phenotype of res adult plants by increasing their sugar content and fruit yield. Together, these results propose an unprecedented role of a DEAD-box RNA helicase in regulating plant development and stress response through the proper ribosome and chloroplast functioning, which, in turn, represents a potential target to improve salt tolerance in tomato crops.  相似文献   
109.
110.
Hydrobiologia - Integrative approaches are particularly useful to resolve taxonomic uncertainties in species-rich groups that have undergone explosive radiation, such as Hypostomini (suckermouth...  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