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   1981篇
  免费   272篇
  国内免费   1篇
  2024年   5篇
  2023年   18篇
  2022年   42篇
  2021年   106篇
  2020年   70篇
  2019年   79篇
  2018年   104篇
  2017年   89篇
  2016年   140篇
  2015年   162篇
  2014年   157篇
  2013年   181篇
  2012年   144篇
  2011年   139篇
  2010年   127篇
  2009年   76篇
  2008年   70篇
  2007年   71篇
  2006年   57篇
  2005年   55篇
  2004年   45篇
  2003年   34篇
  2002年   38篇
  2001年   22篇
  2000年   21篇
  1999年   21篇
  1997年   12篇
  1996年   6篇
  1995年   8篇
  1994年   4篇
  1992年   4篇
  1991年   6篇
  1990年   4篇
  1989年   6篇
  1988年   10篇
  1987年   7篇
  1986年   6篇
  1985年   9篇
  1984年   9篇
  1983年   11篇
  1982年   8篇
  1981年   4篇
  1980年   4篇
  1979年   3篇
  1977年   3篇
  1975年   4篇
  1974年   3篇
  1973年   4篇
  1971年   5篇
  1857年   4篇
排序方式: 共有2254条查询结果,搜索用时 31 毫秒
101.
GskA, the Dictyostelium GSK-3 orthologue, is modified and activated by the dual-specificity tyrosine kinase Zak1, and the two kinases form part of a signaling pathway that responds to extracellular cyclic AMP. We identify potential cellular effectors for the two kinases by analyzing the corresponding null mutants. There are proteins and mRNAs that are altered in abundance in only one or the other of the two mutants, indicating that each kinase has some unique functions. However, proteomic and microarray analyses identified a number of proteins and genes, respectively, that are similarly misregulated in both mutant strains. The positive correlation between the array data and the proteomic data is consistent with the Zak1-GskA signaling pathway's functioning by directly or indirectly regulating gene expression. The discoidin 1 genes are positively regulated by the pathway, while the abundance of the H5 protein is negatively regulated. Two of the targets, H5 and discoidin 1, are well-characterized markers for early development, indicating that the Zak1-GskA pathway plays a role in development earlier than previously observed.  相似文献   
102.

In this report, a novel D-shaped long-range surface plasmon resonance (LRSPR) fiber base sensor has been introduced. The demonstration of proposed sensor involves two D-shaped silver-coated models to study the sensitivity responses. The entire study with the constructed models is based on a single-mode fiber. The models are multilayered consisting of metal, dielectric, and analyte as separate layers. Silver (Ag) and magnesium fluoride (MgF2) strips are used as metal and dielectric layers respectively. The constituency of analyte as an interface excellently standardized the models for sensitivity detection. In this report, a large range of analyte refractive indices (RI) which varies from 1.33 to 1.38 is appraised for the proposed models to characterize the sensitivity. The entire context is encompassed by the wavelength region from 450 to 850 nm with an interval of 20 nm. Sensitivities in this report are measured based on the analyte position from the core and metal for both models. For each of the two models, the analyte is placed as the top layer. RIs of the applied metal (Ag) are measured using the Drude-Lorentz formula. The simulated sensitivities for model-1 and model-2 vary from 6.3?×?103 nm/RIU to 8.7?×?103 nm/RIU.

  相似文献   
103.
Autophagy is a preserved cytoplasmic self-degradation process and endorses recycling of intracellular constituents into bioenergetics for the controlling of cellular homeostasis. Functional autophagy process is essential in eliminating cytoplasmic waste components and helps in the recycling of some of its constituents. Studies have revealed that neurodegenerative disorders may be caused by mutations in autophagy-related genes and alterations of autophagic flux. Alzheimer’s disease (AD) is an irrevocable deleterious neurodegenerative disorder characterized by the formation of senile plaques and neurofibrillary tangles (NFTs) in the hippocampus and cortex. In the central nervous system of healthy people, there is no accretion of amyloid β (Aβ) peptides due to the balance between generation and degradation of Aβ. However, for AD patients, the generation of Aβ peptides is higher than lysis that causes accretion of Aβ. Likewise, the maturation of autophagolysosomes and inhibition of their retrograde transport creates favorable conditions for Aβ accumulation. Furthermore, increasing mammalian target of rapamycin (mTOR) signaling raises tau levels as well as phosphorylation. Alteration of mTOR activity occurs in the early stage of AD. In addition, copious evidence links autophagic/lysosomal dysfunction in AD. Compromised mitophagy is also accountable for dysfunctional mitochondria that raises Alzheimer’s pathology. Therefore, autophagic dysfunction might lead to the deposit of atypical proteins in the AD brain and manipulation of autophagy could be considered as an emerging therapeutic target. This review highlights the critical linkage of autophagy in the pathogenesis of AD, and avows a new insight to search for therapeutic target for blocking Alzheimer’s pathogenesis.  相似文献   
104.
Plant Cell, Tissue and Organ Culture (PCTOC) - The effect of several parameters on trans-resveratrol extracellular production in Vitis vinifera cv Monastrell suspension cultured cells elicited with...  相似文献   
105.
106.
We aimed to study the fecundity and reproductive investment of Loxopagurus loxochelis under different environmental conditions. In total, 67 ovigerous females were analyzed, 20 from Macaé, 26 from Ubatuba and 21 from Cananéia. The cephalothoracic shield length, fecundity and reproductive investment (Ubatuba 10.2%, Macaé 8.9% and Cananéia 7.5%) were different among the regions (ANCOVA, p < 0.05), caused by different abiotic resources and environmental characteristics found in each sampling region. Cananéia had the smallest individuals and low availability of adequate shells to hermit crabs, a condition that may have affected the growth and reproduction of the animals. Macaé has a continuous transport of nutrients such as nitrogen and phosphorus to the surface promoted by the Cabo Frio Upwelling zone, which may be a favourable condition for plankton production and, consequently, the extended ‘match/mismatch’ adjustment of spawning females of L. loxochelis. We propose that the highest reproductive investment on the Ubatuba coast is a consequence of regional environmental scenarios of waters colder than the Cananéia region, i.e. females concentrate more energy to reproduce seasonally. Thus, we proved that patterns of L. loxochelis’ reproduction can change on a regional scale according to the local condition of shell supply and water temperature.  相似文献   
107.
Nigella sativa (NS) has been shown to have antioxidant and antiinflammatory activities in different conditions. The goal of this study was to evaluate the effects of NS on cholestatic liver injury in rats. Thirty rats were recruited in the study as follows: Group 1, Bile duct ligation (BDL) (n = 10); Group 2, BDL plus NS (n = 10); and Group 3, Sham (n = 10). Bile duct ligated group received 0.2 mL kg?1 dose of NS intraperitoneally daily throughout 14 days. Liver damage and cholestasis were determined by the biochemical and the pathologic examination. Data showed a decrease in gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) activities of the NS treated rats when compared with BDL group (p < 0.001 for GGT and p < 0.05 for others). The NS treated rats' tissue levels of total oxidant status (TOS), oxidative stress index (OSI), and myeloperoxidase (MPO) were significantly lower than that of the BDL group (p < 0.01 for all). Increases in total antioxidant capacity (TAC) and catalase (CAT) levels were statistically significant in the NS treated rats compared to BDL group (p < 0.01 for both). On the other hand, administration of NS in the rats with biliary obstruction resulted in inhibition of necro‐inflammation. These results indicate that NS exerts a therapeutic effect on cholestatic liver injury in bile duct ligated rats possibly through attenuation of enhanced neutrophil infiltration and oxidative stress in the liver tissue. Copyright © 2009 John Wiley & Sons, Ltd.  相似文献   
108.
AIMS: Isolation and characterization of Streptococcus bovis from the dromedary camel and Rusa deer. METHODS AND RESULTS: Bacteria were isolated from the rumen contents of four camels and two deer fed lucerne hay by culturing on the semi-selective medium MRS agar. Based on Gram morphology and RFLP analysis seven isolates, MPR1, MPR2, MPR3, MPR4, MPR5, RD09 and RD11 were selected and putatively identified as Streptococcus. The identity of these isolates was later confirmed by comparative DNA sequence analysis of the 16S rRNA gene with the homologous sequence from S. bovis strains, JB1, C14b1, NCFB2476, SbR1, SbR7 and Sb5, from cattle and sheep, and the Streptococcus equinus strain NCD01037T. The percentage similarity amongst all strains was >99%, confirming the identification of the camel isolates as S. bovis. The strains were further characterized by their ability to utilize a range of carbohydrates, the production of volatile fatty acids (VFA) and lactate and the determination of the doubling time in basal medium 10 supplemented with glucose. All the isolates produced l-lactate as a major fermentation end product, while four of five camel isolates produced VFA. The range of carbohydrates utilized by all the strains tested, including those from cattle and sheep were identical, except that all camel isolates and the deer isolate RD11 were additionally able to utilize arabinose. CONCLUSIONS: Streptococcus bovis was successfully isolated from the rumen of camels and deer, and shown by molecular and biochemical characterization to be almost identical to S. bovis isolates from cattle and sheep. SIGNIFICANCE AND IMPACT OF THE STUDY: Streptococcus bovis is considered a key lactic acid producing bacterium from the gastrointestinal tract of ruminants, and has been implicated as a causative agent of lactic acidosis. This study is the first report of the isolation and characterization of S. bovis from the dromedary camel and Rusa deer, and suggests a major contributive role of this bacterium to fermentative acidosis.  相似文献   
109.
Type III secretion systems identified in bacterial pathogens of animals and plants transpose effectors and toxins directly into the cytosol of host cells or into the extracellular milieu. Proteins of the type III secretion apparatus are conserved among diverse and distantly related bacteria. Many type III apparatus proteins have homologues in the flagellar export apparatus, supporting the notion that type III secretion systems evolved from the flagellar export apparatus. No type III secretion apparatus genes have been found in the complete genomic sequence of Campylobacter jejuni NCTC11168. In this study, we report the characterization of a protein designated FlaC of C. jejuni TGH9011. FlaC is homologous to the N- and C-terminus of the C. jejuni flagellin proteins, FlaA and FlaB, but lacks the central portion of these proteins. flaC null mutants form a morphologically normal flagellum and are highly motile. In wild-type C. jejuni cultures, FlaC is found predominantly in the extracellular milieu as a secreted protein. Null mutants of the flagellar basal rod gene (flgF) and hook gene (flgE) do not secrete FlaC, suggesting that a functional flagellar export apparatus is required for FlaC secretion. During C. jejuni infection in vitro, secreted FlaC and purified recombinant FlaC bind to HEp-2 cells. Invasion of HEp-2 cells by flaC null mutants was reduced to a level of 14% compared with wild type, suggesting that FlaC plays an important role in cell invasion.  相似文献   
110.
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