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   1615篇
  免费   233篇
  2023年   12篇
  2022年   13篇
  2021年   33篇
  2020年   15篇
  2019年   26篇
  2018年   35篇
  2017年   28篇
  2016年   39篇
  2015年   66篇
  2014年   83篇
  2013年   102篇
  2012年   117篇
  2011年   92篇
  2010年   67篇
  2009年   53篇
  2008年   65篇
  2007年   65篇
  2006年   65篇
  2005年   61篇
  2004年   45篇
  2003年   48篇
  2002年   61篇
  2001年   44篇
  2000年   45篇
  1999年   35篇
  1998年   27篇
  1997年   21篇
  1996年   21篇
  1995年   11篇
  1994年   18篇
  1993年   19篇
  1992年   16篇
  1991年   23篇
  1990年   19篇
  1989年   14篇
  1988年   14篇
  1987年   11篇
  1986年   15篇
  1985年   17篇
  1984年   17篇
  1983年   10篇
  1982年   14篇
  1979年   8篇
  1978年   10篇
  1977年   11篇
  1975年   16篇
  1974年   18篇
  1973年   8篇
  1970年   9篇
  1907年   7篇
排序方式: 共有1848条查询结果,搜索用时 15 毫秒
991.
Irrespective of its causes, strong population genetic structure indicates a lack of gene flow. Understanding the processes that underlie such structure, and the spatial patterns it causes, is valuable for conservation efforts such as restoration. On the other hand, when a species is invasive outside its native range, such information can aid management in the non-native range. Here we explored the genetic characteristics of the Australian tree Acacia dealbata in its native range. Two subspecies of A. dealbata have previously been described based on morphology and environmental requirements, but recent phylogeographic data raised questions regarding the validity of this taxonomic subdivision. The species has been widely planted within and outside its native Australian range and is also a highly successful invasive species in many parts of the world. We employed microsatellite markers to investigate the population genetic diversity and structure among 42 A. dealbata populations from across the species’ native range. We also tested whether environmental variables purportedly relevant for the putative separation of subspecies are linked with population genetic differentiation. We found no relationship between population genetic structure of A. dealbata in Australia and these environmental features. Rather, we identified two geographically distinct genetic clusters that corresponded with populations in the northeastern part of mainland Australia, and the southern mainland and Tasmanian range of the species. Our results do not support the taxonomic subdivision of the species into two distinct subspecies based on environmental features. We therefore assume that the observed morphological differences between the putative subspecies are plastic phenotypic responses. This study provides population genetic information that will be useful for the conservation of the species within Australia as well as to better understand the invasion dynamics of A. dealbata.  相似文献   
992.
Whole genome sequencing is helping generate robust phylogenetic hypotheses for a range of taxonomic groups that were previously recalcitrant to classical molecular phylogenetic approaches. As a case study, we performed a shallow shotgun sequencing of eight species in the tropical tree family Chrysobalanaceae to retrieve large fragments of high‐copy number DNA regions and test the potential of these regions for phylogeny reconstruction. We were able to assemble the nuclear ribosomal cluster (nrDNA), the complete plastid genome (ptDNA) and a large fraction of the mitochondrial genome (mtDNA) with approximately 1000×, 450× and 120× sequencing depth respectively. The phylogenetic tree obtained with ptDNA resolved five of the seven internal nodes. In contrast, the tree obtained with mtDNA and nrDNA data were largely unresolved. This study demonstrates that genome skimming is a cost‐effective approach and shows potential in plant molecular systematics within Chrysobalanaceae and other under‐studied groups.  相似文献   
993.

Background

18Fluor-deoxy-glucose PET-scanning of glycolytic metabolism is being used for staging in many tumors however its impact on prognosis has never been studied in breast cancer.

Methods

Glycolytic and hypoxic markers: glucose transporter (GLUT1), carbonic anhydrase IX (CAIX), monocarboxylate transporter 1 and 4 (MCT1, 4), MCT accessory protein basigin and lactate-dehydrogenase A (LDH-A) were assessed by immunohistochemistry in two cohorts of breast cancer comprising 643 node-negative and 127 triple negative breast cancers (TNBC) respectively.

Results

In the 643 node-negative breast tumor cohort with a median follow-up of 124 months, TNBC were the most glycolytic (≈70%), followed by Her-2 (≈50%) and RH-positive cancers (≈30%). Tumoral MCT4 staining (without stromal staining) was a strong independent prognostic factor for metastasis-free survival (HR = 0.47, P = 0.02) and overall-survival (HR = 0.38, P = 0.002). These results were confirmed in the independent cohort of 127 cancer patients.

Conclusion

Glycolytic markers are expressed in all breast tumors with highest expression occurring in TNBC. MCT4, the hypoxia-inducible lactate/H+ symporter demonstrated the strongest deleterious impact on survival. We propose that MCT4 serves as a new prognostic factor in node-negative breast cancer and can perhaps act soon as a theranostic factor considering the current pharmacological development of MCT4 inhibitors.  相似文献   
994.
The conventional model of polymeric IgM depicts a unique structure in which the mu heavy chains and J chain are joined by well defined disulfide bonds involving cysteine residues at positions 337, 414 and 575 of the mu chain. To test this model, we have used site directed mutagenesis to produce IgM in which these cysteines have been replaced by serine. In each case the single mutants were able to assemble polymeric IgM, which was analyzed for its size, morphology, J chain content and activity in complement dependent cytolysis. Whereas normal polymeric IgM is composed predominantly of pentameric and hexameric molecules, the mutant IgM-Ser414 is covalently assembled as pentamers and smaller forms; IgM-Ser575 is assembled as covalent hexamers. IgM-Ser337 appears to include the same pentameric and hexameric forms as normal IgM except that, unlike normal polymeric IgM, most pentameric/hexameric IgM-Ser337 is not covalently assembled. J chain is present in polymeric IgM-Ser337 but absent in polymeric IgM-Ser414 and IgM-Ser575. IgM-Ser414 is defective in activating the classical pathway of complement dependent cytolysis. Our observations are consistent with models in which the covalent linkages between mu chains are mediated by disulfide bonded Cys337-Cys337, Cys414-Cys414 and Cys575-Cys575 but indicate that the arrangement of these Cys-Cys pairs in series and in parallel varies among and within IgM molecules.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   
995.
The HIV-1 encoded apoptogenic protein Vpr induces mitochondrial membrane permeabilization (MMP) via interactions with the voltage-dependent anion channel (VDAC) and the adenine nucleotide translocator (ANT). We have designed a peptide, TEAM-VP, composed of two functional domains, one a tumor blood vessel RGD-like 'homing' motif and the other an MMP-inducing sequence derived from Vpr. When added to isolated mitochondria, TEAM-VP interacts with ANT and VDAC, reduces oxygen consumption and overcomes Bcl-2 protection to cause inner and outer MMP. TEAM-VP specifically recognizes cell-surface expressed alpha(V)beta(3) integrins, internalizes, temporarily localizes to lysosomes and progressively co-distributes with the mitochondrial compartment with no sign of lysosomal membrane permeabilization. Finally TEAM-VP reaches mitochondria of angiogenic endothelial cells to induce mitochondrial fission, dissipation of the mitochondrial transmembrane potential (DeltaPsi(m)), cytochrome c release and apoptosis hallmarks. Hence, this chimeric peptide constitutes the first example of a virus-derived mitochondriotoxic compound as a candidate to kill selectively tumor neo-endothelia.  相似文献   
996.
997.
998.
The Asian Long‐horned Beetle (ALB) is a highly polyphagous species invasive in North America and Europe. This species has been reported to have low dispersing potential, but long‐distance dispersal could occasionally happen. We conducted a preliminary study on laboratory‐reared adults from invasive populations to measure the flying potential of beetles using computer‐linked flight mills. Under standardized conditions, ALB was capable of flying over longer distances than previously described. The highest distance recorded over an adult lifespan outreached 14 km. Flight mill method is therefore useful to estimate the maximum physiological flight abilities of the species that should be taken into account to improve management of invasive populations.  相似文献   
999.
A START POINT FOR EXTRACELLULAR NUCLEOTIDE SIGNALING
The recent discovery of a plant receptor for extracellu- lar nucleotides, reported by Choi et al. (2014), is a major breakthrough that had been anticipated for over a dec- ade. Plants release ATP into their extracellular matrix (ECM) during growth and when they are induced by vari- ous biotic and abiotic stimuli (Clark and Roux, 2011). That these extracellular nucleotides would activate receptors in plants was predicted by two sets of discoveries: that low- and sub-micromolar ATP could induce increases in [Ca2+]cyt, NO, and superoxide signaling intermediates that led to downstream growth, stomatal, and defense responses, and that these changes could be blocked by antagonists that blocked extracellular nucleotide receptors in animals (Demidchik et al., 2003; Song et al., 2006; Clark et al., 2011; Demidchik et al., 2009, 2011). Although mammalian biolo- gists had discovered two classes of receptors for extracel- lular nucleotides (P2X and P2Y) decades ago (Burnstock, 2007), there were no plant proteins obviously similar to these in any sequence data available. Clearly, if there were plant purinoceptors, they would be different from the mammalian receptors, and they could not be discovered by motif searches.  相似文献   
1000.
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