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   1221篇
  免费   177篇
  2022年   11篇
  2021年   14篇
  2020年   10篇
  2019年   11篇
  2017年   14篇
  2016年   20篇
  2015年   30篇
  2014年   38篇
  2013年   57篇
  2012年   69篇
  2011年   67篇
  2010年   39篇
  2009年   40篇
  2008年   55篇
  2007年   59篇
  2006年   47篇
  2005年   56篇
  2004年   33篇
  2003年   36篇
  2002年   40篇
  2001年   40篇
  2000年   36篇
  1999年   24篇
  1998年   22篇
  1997年   13篇
  1996年   25篇
  1995年   17篇
  1994年   9篇
  1993年   16篇
  1992年   24篇
  1991年   34篇
  1990年   32篇
  1989年   26篇
  1988年   25篇
  1987年   20篇
  1986年   10篇
  1985年   19篇
  1984年   17篇
  1983年   16篇
  1981年   11篇
  1980年   16篇
  1979年   12篇
  1978年   20篇
  1977年   13篇
  1976年   10篇
  1975年   25篇
  1974年   16篇
  1973年   14篇
  1972年   11篇
  1969年   9篇
排序方式: 共有1398条查询结果,搜索用时 31 毫秒
51.
The biomass and production of the most important zooplankton species were followed for two years in three lakes of varying trophic status in the Lake Washington watershed. Cladocerans and copepods were of equal importance in the biomass of lakes Findley and Chester Morse (both oligotrophic), whereas, copepods were the main biomass component in Lake Sammamish (mesotrophic). Cladocerans dominated production in lakes Sammamish and Chester Morse, while in Findley Lake their productive role, like that of biomass, was equal to that of the copepods. Rotifers contributed a relatively small biomass and production.Data from this study supported Hillbricht-Ilkowska's postulate that the energy transfer efficiency between the primary and secondary trophic levels decreases with increasing trophic state. Energy transfer efficiencies for the lakes of this study expressed as a two year mean of the ratio-secondary: primary production, were as follows: Findley Lake-0.13; Chester Morse Lake-0.08; and Lake Sammanish-0.04.On the other hand, the hypothesis of Patalas that the secondary productivity: biomass ratio (P/B) tended to increase in proportion to the productivity of a lake, could not be supported. Lake Sammamish, the most productive of the lakes studied, had a P/B ratio of 0.03 while lakes Findley and Chester Morse had P/B ratios of 0.04.  相似文献   
52.
Adenocarcinoma of the oesophagus and gastro-oesophageal junction are rapidly increasing in incidence and have a well described sequence of carcinogenesis: the Barrett's metaplasia-dysplasia-adenocarcinoma sequence. During recent years there have been changes in the knowledge surrounding disease progression, cancer management and histopathology specimen reporting. Tumours around the gastro-oesophageal junction (GOJ) pose several specific challenges. Numerous difficulties arise when the existing TNM staging systems for gastric and oesophageal cancers are applied to GOJ tumours. The issues facing the current TNM staging and GOJ tumour classification systems are reviewed in this article. Recent evidence regarding the importance of several histopathologically derived prognostic factors, such as circumferential resection margin status and lymph node metastases, have implications for specimen reporting. With the rising use of multimodal treatments for oesophageal cancer it is important that the response of the tumour to this therapy is carefully documented pathologically. In addition, several controversial and novel areas such as endoscopic mucosal resection, lymph node micrometastases and the sentinel node concept are being studied. We aim to review these aspects, with special relevance to oesophageal and gastro-oesophageal cancer specimen reporting, to update the surgical oncologist with an interest in upper gastrointestinal cancer.  相似文献   
53.
Mammalian ovarian follicular development is tightly regulated by crosstalk between cell death and survival signals, which include both endocrine and intra-ovarian regulators. Whether the follicle ultimately ovulates or undergoes atresia is dependent on the expression and actions of factors promoting follicular cell proliferation, differentiation or apoptosis. Prohibitin (PHB) is a highly conserved, ubiquitous protein that is abundantly expressed in granulosa cells (GCs) and associated with GC differentiation and apoptosis. The current study was designed to characterize the regulation of anti-apoptotic and pro-apoptotic factors in undifferentiated rat GCs (gonadotropin independent phase) governed by PHB. Microarray technology was initially employed to identify potential apoptosis-related genes, whose expression levels within GCs were altered by either staurosporine (STS) alone or STS in presence of ectopically over-expressed PHB. Next, immunoblot studies were performed to examine the expression patterns of selective Bcl-2 family members identified by the microarray analysis, which are commonly regulated in the intrinsic-apoptotic pathway. These studies were designed to measure protein levels of Bcl2 family in relation to expression of the acidic isoform (phosphorylated) PHB and the components of MEK-Erk1/2 pathway. These studies indicated that over-expression of PHB in undifferentiated GCs inhibit apoptosis which concomitantly results in an increased level of the anti-apoptotic proteins Bcl2 and Bclxl, reduced release of cytochrome c from mitochondria and inhibition of caspase-3 activity. In contrast, silencing of PHB expression resulted in change of mitochondrial morphology from the regular reticular network to a fragmented form, which enhanced sensitization of these GCs to the induction of apoptosis. Collectively, these studies have provided new insights on the PHB-mediated anti-apoptotic mechanism, which occurs in undifferentiated GCs through a PHB → Mek-Erk1/2 → Bcl/Bcl-xL pathway and may have important clinical implications.  相似文献   
54.
Paramyxoviruses cause a wide variety of human and animal diseases. They infect host cells using the coordinated action of two surface glycoproteins, the receptor binding protein (HN, H, or G) and the fusion protein (F). HN binds sialic acid on host cells (hemagglutinin activity) and hydrolyzes these receptors during viral egress (neuraminidase activity, NA). Additionally, receptor binding is thought to induce a conformational change in HN that subsequently triggers major refolding in homotypic F, resulting in fusion of virus and target cell membranes. HN is an oligomeric type II transmembrane protein with a short cytoplasmic domain and a large ectodomain comprising a long helical stalk and large globular head domain containing the enzymatic functions (NA domain). Extensive biochemical characterization has revealed that HN-stalk residues determine F specificity and activation. However, the F/HN interaction and the mechanisms whereby receptor binding regulates F activation are poorly defined. Recently, a structure of Newcastle disease virus (NDV) HN ectodomain revealed the heads (NA domains) in a “4-heads-down” conformation whereby two of the heads form a symmetrical interaction with two sides of the stalk. The interface includes stalk residues implicated in triggering F, and the heads sterically shield these residues from interaction with F (at least on two sides). Here we report the x-ray crystal structure of parainfluenza virus 5 (PIV5) HN ectodomain in a “2-heads-up/2-heads-down” conformation where two heads (covalent dimers) are in the “down position,” forming a similar interface as observed in the NDV HN ectodomain structure, and two heads are in an “up position.” The structure supports a model in which the heads of HN transition from down to up upon receptor binding thereby releasing steric constraints and facilitating the interaction between critical HN-stalk residues and F.  相似文献   
55.
Using mitochondrial DNA for species identification and population studies assumes that the genome is maternally inherited, circular, located in the cytoplasm and lacks recombination. This study explores the mitochondrial genomes of three anomalous mackerel. Complete mitochondrial genome sequencing plus nuclear microsatellite genotyping of these fish identified them as Scomberomorus munroi (spotted mackerel). Unlike normal S. munroi, these three fish also contained different linear, mitochondrial genomes of Scomberomorus semifasciatus (grey mackerel). The results are best explained by hybridisation, paternal leakage and mitochondrial DNA linearization. This unusual observation may provide an explanation for mtDNA outliers in animal population studies.  相似文献   
56.
Community-acquired urinary tract infections (UTIs) are commonly caused by uropathogenic Escherichia coli (UPEC). We hypothesize that chemotaxis toward ligands present in urine could direct UPEC into and up the urinary tract. Wild-type E. coli CFT073 and chemoreceptor mutants with tsr, tar, or aer deletions were tested for chemotaxis toward human urine in the capillary tube assay. Wild-type CFT073 was attracted toward urine, and Tsr and Tar were the chemoreceptors mainly responsible for mediating this response. The individual components of urine including L-amino acids, D-amino acids and various organic compounds were also tested in the capillary assay with wild-type CFT073. Our results indicate that CFT073 is attracted toward some L- amino acids and possibly toward some D-amino acids but not other common compounds found in urine such as urea, creatinine and glucuronic acid. In the murine model of UTI, the loss of any two chemoreceptors did not affect the ability of the bacteria to compete with the wild-type strain. Our data suggest that the presence of any strong attractant and its associated chemoreceptor might be sufficient for colonization of the urinary tract and that amino acids are the main chemoattractants for E. coli strain CFT073 in this niche.  相似文献   
57.
When divergent populations form hybrids, hybrid fitness can vary with genome composition, current environmental conditions, and the divergence history of the populations. We develop analytical predictions for hybrid fitness, which incorporate all three factors. The predictions are based on Fisher's geometric model, and apply to a wide range of population genetic parameter regimes and divergence conditions, including allopatry and parapatry, local adaptation, and drift. Results show that hybrid fitness can be decomposed into intrinsic effects of admixture and heterozygosity, and extrinsic effects of the (local) adaptedness of the parental lines. Effect sizes are determined by a handful of geometric distances, which have a simple biological interpretation. These distances also reflect the mode and amount of divergence, such that there is convergence toward a characteristic pattern of intrinsic isolation. We next connect our results to the quantitative genetics of line crosses in variable or patchy environments. This means that the geometrical distances can be estimated from cross data, and provides a simple interpretation of the “composite effects.” Finally, we develop extensions to the model, involving selectively induced disequilibria, and variable phenotypic dominance. The geometry of fitness landscapes provides a unifying framework for understanding speciation, and wider patterns of hybrid fitness.  相似文献   
58.
In this study we describe the evaluation of a recently developed supercritical fluid chromatography (SFC) instrument for automated chiral SFC method development. The greatly improved gradient dwell volume and liquid flow control of the new instrument in combination with the use of shorter columns containing smaller stationary phase particles affords chiral SFC method development that is faster and more universal than previous systems. Chirality 25:799–804, 2013. © 2013 Wiley Periodicals, Inc.  相似文献   
59.
The dissolution rate of apatite was determined in batch reactors in organic acid solutions and in microbial cultures. Inoculum for the cultures was from biotite plus apatite crystals from a granite weathering profile in South Eastern Australia. In both the biotic and the abiotic experiments, etching of the apatite surface leads to the formation of elongated spires parallel to the c axis. Apatite dissolution rates in the inorganic, acetate, and oxalate solutions increase as pH decreases from approximately 10 -11 mol/m -2 · s -1 at initial pH 5.5 to 10 -7 mol/m -2 · s -1 at initial pH 2. Under mildly acidic to near neutral pH conditions, both oxalate and acetate increased apatite dissolution by up to an order of magnitude compared to the inorganic conditions. Acetate catalyzed the reaction by forming complexes with Ca, either in solution or at the mineral surfaces. Oxalate forms complexes with Ca as well, and can also affect reaction rates and stoichiometry by forming Ca-oxalate precipitates, thus affecting solution saturation states. In all abiotic experiments, net phosphate release to solution approaches zero even when solutions are apparently undersaturated by several orders of magnitude with respect to the solubility of an ideal fluoroapatite mineral. In the microbial experiments, two enrichment cultures increased both apatite and biotite dissolution by producing organic acids, primarily pyruvate, fermentation products, and oxalate, and by lowering bulk solution pH to between 3 and 5. However, the microorganisms were also able to increase phosphate release from apatite (by two orders of magnitude) without lowering bulk solution pH by producing pyruvate and other compounds.  相似文献   
60.
NtrYX is a sensor-histidine kinase/response regulator two-component system that has had limited characterization in a small number of Alphaproteobacteria. Phylogenetic analysis of the response regulator NtrX showed that this two-component system is extensively distributed across the bacterial domain, and it is present in a variety of Betaproteobacteria, including the human pathogen Neisseria gonorrhoeae. Microarray analysis revealed that the expression of several components of the respiratory chain was reduced in an N. gonorrhoeae ntrX mutant compared to that in the isogenic wild-type (WT) strain 1291. These included the cytochrome c oxidase subunit (ccoP), nitrite reductase (aniA), and nitric oxide reductase (norB). Enzyme activity assays showed decreased cytochrome oxidase and nitrite reductase activities in the ntrX mutant, consistent with microarray data. N. gonorrhoeae ntrX mutants had reduced capacity to survive inside primary cervical cells compared to the wild type, and although they retained the ability to form a biofilm, they exhibited reduced survival within the biofilm compared to wild-type cells, as indicated by LIVE/DEAD staining. Analyses of an ntrX mutant in a representative alphaproteobacterium, Rhodobacter capsulatus, showed that cytochrome oxidase activity was also reduced compared to that in the wild-type strain SB1003. Taken together, these data provide evidence that the NtrYX two-component system may be a key regulator in the expression of respiratory enzymes and, in particular, cytochrome c oxidase, across a wide range of proteobacteria, including a variety of bacterial pathogens.  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