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   3490篇
  免费   297篇
  国内免费   7篇
  3794篇
  2023年   21篇
  2022年   27篇
  2021年   48篇
  2020年   36篇
  2019年   46篇
  2018年   68篇
  2017年   46篇
  2016年   100篇
  2015年   151篇
  2014年   194篇
  2013年   220篇
  2012年   298篇
  2011年   269篇
  2010年   146篇
  2009年   154篇
  2008年   199篇
  2007年   182篇
  2006年   154篇
  2005年   139篇
  2004年   139篇
  2003年   131篇
  2002年   126篇
  2001年   104篇
  2000年   61篇
  1999年   89篇
  1998年   29篇
  1997年   26篇
  1996年   23篇
  1995年   22篇
  1994年   24篇
  1993年   20篇
  1992年   50篇
  1991年   33篇
  1990年   39篇
  1989年   32篇
  1988年   40篇
  1987年   34篇
  1986年   35篇
  1985年   23篇
  1984年   14篇
  1983年   14篇
  1981年   13篇
  1980年   12篇
  1979年   26篇
  1978年   13篇
  1977年   11篇
  1976年   14篇
  1975年   12篇
  1974年   19篇
  1972年   12篇
排序方式: 共有3794条查询结果,搜索用时 15 毫秒
991.
In this revision, three species are recognised. A discussion is made on merging the genus Polysolenia into Leptomischus. Indopolysolenia burmanica Deb et Rout is reduced to a synonum of Leptomischus primuloides Drake. A key to species is given below: l. Flowers larger, with corollas more than 2cm long. 2.Stipules 3-fid or torn; Leaves narrowly lanceolate; stigmas with 2 short obtuse lobes ...................................................... 1.L. wallichii 2.Stipules entire; leaves obovate to elliptic; stigmas with 2 slender elongate lobes ......................................................... 2. L. primuloides 1.Flowers smaller, with corollas 6-6.5mm long; stigmas with 2 lanceolate lobes .......................................................... 3. L. parviflorus  相似文献   
992.
993.
Mitochondria are the major organelles in sensing cellular stress and inducing the response for cell survival. Mitochondrial Lon has been identified as an important stress protein involved in regulating proliferation, metastasis, and apoptosis in cancer cells. However, the mechanism of retrograde signaling by Lon on mitochondrial DNA (mtDNA) damage remains to be elucidated. Here we report the role of Lon in the response to cisplatin-induced mtDNA damage and oxidative stress, which confers cancer cells on cisplatin resistance via modulating calcium levels in mitochondria and cytosol. First, we found that cisplatin treatment on oral cancer cells caused oxidative damage of mtDNA and induced Lon expression. Lon overexpression in cancer cells decreased while Lon knockdown sensitized the cytotoxicity towards cisplatin treatment. We further identified that cisplatin-induced Lon activates the PYK2-SRC-STAT3 pathway to stimulate Bcl-2 and IL-6 expression, leading to the cytotoxicity resistance to cisplatin. Intriguingly, we found that activation of this pathway is through an increase of intracellular calcium (Ca2+) via NCLX, a mitochondrial Na+/Ca2+ exchanger. We then verified that NCLX expression is dependent on Lon levels; Lon interacts with and activates NCLX activity. NCLX inhibition increased the level of mitochondrial calcium and sensitized the cytotoxicity to cisplatin in vitro and in vivo. In summary, mitochondrial Lon-induced cisplatin resistance is mediated by calcium release into cytosol through NCLX, which activates calcium-dependent PYK2-SRC-STAT3-IL-6 pathway. Thus, our work uncovers the novel retrograde signaling by mitochondrial Lon on resistance to cisplatin-induced mtDNA stress, indicating the potential use of Lon and NCLX inhibitors for better clinical outcomes in chemoresistant cancer patients.Subject terms: Cancer therapeutic resistance, Mitochondria, Calcium and vitamin D  相似文献   
994.
An intracellular bacterium from Ixodes ricinus ticks collected in Italy was characterized by electron microscopy (EM), PCR sequencing of the 16S rRNA gene, molecular phylogenetic analysis, and in situ hybridization (ISH). This bacterium was shown by EM to be present in the cytoplasm, as well as in the mitochondria of ovarian cells. When universal 16S rRNA bacterial primers were used, PCR amplification of ovarian DNA followed by cloning and sequencing resulted in the same sequence being found in each sample. Phylogenetic analysis of this sequence showed that the bacterium from which it was derived, tentatively designated IricES1, is part of a novel clade in the alpha subdivision of the Proteobacterium: ISH and PCR assays of various tissues performed with oligonucleotides specific for the IricES1 16S rRNA showed that IricES1 is restricted to ovarian cells. Based on the results obtained, we inferred that the bacteria seen by EM in ovarian cells are a single type of bacteria, corresponding to IricES1. PCR screening of 166 ticks from various parts of Italy and one site in England showed that IricES1 was present in 96% of adult females and 44% of nymphs (unsexed). No adult males were found to be infected. Despite the apparent parasitism of host mitochondria by IricES1, the available information suggests that the bacterium has an obligate relationship with its host, although this must be confirmed.  相似文献   
995.
Changes in leaf hydraulic conductance (K) were measured using the vacuum chamber technique during dehydration and rehydration of potted plants of Ceratonia siliqua . K of whole, compound leaves as well as that of rachides and leaflets decreased by 20–30% at leaf water potentials (ΨL) of −1.5 and −2.0 MPa, i.e. at ΨL values commonly recorded in field-growing plants of the species. Higher K losses (up to 50%) were measured for leaves at ΨL of −2.5 and −3.0 MPa, i.e. near or beyond the leaf turgor loss point. Leaves of plants rehydrated while in the dark for 30 min, 90 min and 12 h recovered from K loss with characteristic times and to extents inversely proportional to the initial water stress applied. Leaf conductance to water vapour of plants dehydrated to decreasing ΨL and rehydrated at low transpiration was inversely related to loss of K, thus suggesting that leaf vein embolism and refilling (and related changes in leaf hydraulics) may play a significant role in the stomatal response.  相似文献   
996.
997.
Senataxin is a large 303 kDa protein linked to neuron survival, as recessive mutations cause Ataxia with Oculomotor Apraxia type 2 (AOA2), and dominant mutations cause amyotrophic lateral sclerosis type 4 (ALS4). Senataxin contains an amino-terminal protein-interaction domain and a carboxy-terminal DNA/RNA helicase domain. In this study, we focused upon the common ALS4 mutation, L389S, by performing yeast two-hybrid screens of a human brain expression library with control senataxin or L389S senataxin as bait. Interacting clones identified from the two screens were collated, and redundant hits and false positives subtracted to yield a set of 13 protein interactors. Among these hits, we discovered a highly specific and reproducible interaction of L389S senataxin with a peptide encoded by the antisense sequence of a brain-specific non-coding RNA, known as BCYRN1. We further found that L389S senataxin interacts with other proteins containing regions of conserved homology with the BCYRN1 reverse complement-encoded peptide, suggesting that such aberrant protein interactions may contribute to L389S ALS4 disease pathogenesis. As the yeast two-hybrid screen also demonstrated senataxin self-association, we confirmed senataxin dimerization via its amino-terminal binding domain and determined that the L389S mutation does not abrogate senataxin self-association. Finally, based upon detection of interactions between senataxin and ubiquitin–SUMO pathway modification enzymes, we examined senataxin for the presence of ubiquitin and SUMO monomers, and observed this post-translational modification. Our senataxin protein interaction study reveals a number of features of senataxin biology that shed light on senataxin normal function and likely on senataxin molecular pathology in ALS4.  相似文献   
998.
999.
Ecosystems are usually complex, nonlinear and strongly influenced by poorly known environmental variables. Among these systems, marine ecosystems have high uncertainties: marine populations in general are known to exhibit large levels of natural variability and the intensity of fishing efforts can change rapidly. These uncertainties are a source of risks that threaten the sustainability of both fish populations and fishing fleets targeting them. Appropriate management measures have to be found in order to reduce these risks and decrease sensitivity to uncertainties. Methods have been developed within decision theory that aim at allowing decision making under severe uncertainty. One of these methods is the information-gap decision theory. The info-gap method has started to permeate ecological modelling, with recent applications to conservation. However, these practical applications have so far been restricted to simple models with analytical solutions. Here we implement a deterministic approach based on decision theory in a complex model of the Eastern English Channel. Using the ISIS-Fish modelling platform, we model populations of sole and plaice in this area. We test a wide range of values for ecosystem, fleet and management parameters. From these simulations, we identify management rules controlling fish harvesting that allow reaching management goals recommended by ICES (International Council for the Exploration of the Sea) working groups while providing the highest robustness to uncertainties on ecosystem parameters.  相似文献   
1000.
A newly developed Enzym Like Immuno Sorbant Assay (ELISA) based on the recombinant nucleocapsid protein (N) of Schmallenberg virus (SBV) was evaluated and validated for the detection of SBV-specific IgG antibodies in ruminant sera by three European Reference Laboratories. Validation data sets derived from sheep, goat and bovine sera collected in France and Germany (n = 1515) in 2011 and 2012 were categorized according to the results of a virus neutralization test (VNT) or an indirect immuno-flurorescence assay (IFA). The specificity was evaluated with 1364 sera from sheep, goat and bovine collected in France and Belgium before 2009. Overall agreement between VNT and ELISA was 98.9% and 98.3% between VNT and IFA, indicating a very good concordance between the different techniques. Although cross-reactions with other Orthobunyavirus from the Simbu serogroup viruses might occur, it is a highly sensitive, specific and robust ELISA-test validated to detect anti-SBV antibodies. This test can be applied for SBV sero-diagnostics and disease-surveillance studies in ruminant species in Europe.  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