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   8922篇
  免费   1074篇
  国内免费   591篇
  2024年   3篇
  2023年   82篇
  2022年   120篇
  2021年   286篇
  2020年   294篇
  2019年   319篇
  2018年   346篇
  2017年   282篇
  2016年   388篇
  2015年   577篇
  2014年   698篇
  2013年   700篇
  2012年   851篇
  2011年   851篇
  2010年   518篇
  2009年   453篇
  2008年   590篇
  2007年   525篇
  2006年   456篇
  2005年   419篇
  2004年   383篇
  2003年   300篇
  2002年   286篇
  2001年   175篇
  2000年   138篇
  1999年   113篇
  1998年   82篇
  1997年   61篇
  1996年   41篇
  1995年   37篇
  1994年   32篇
  1993年   18篇
  1992年   24篇
  1991年   23篇
  1990年   16篇
  1989年   17篇
  1988年   16篇
  1987年   10篇
  1986年   7篇
  1985年   5篇
  1984年   3篇
  1983年   7篇
  1982年   4篇
  1981年   7篇
  1979年   5篇
  1978年   6篇
  1968年   1篇
  1966年   1篇
  1965年   5篇
  1950年   1篇
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
1.
野葛花醇提物中异黄酮含量及其抗氧化活性测定   总被引:2,自引:1,他引:1  
以葛花苷为标准品,对野葛花醇提物的氯仿、乙酸乙酯、正丁醇萃取物及水溶物4部分中的异黄酮含量进行测定,并采用DPPH·法对各萃取物进行自由基清除实验.结果显示,(1)氯仿、乙酸乙酯、正丁醇萃取物及水溶物4部分的异黄酮含量分别为35.27%、53.42%、52.13%和2.34%.(2)抗氧化实验显示, 4 部分清除DPPH·的IC50值分别为252、49、197和344 μg/mL.(3)相关性分析表明,野葛花醇提物各萃取部分的抗氧化活性主要来自于其中含有的异黄酮类化合物.研究表明野葛花醇提物的乙酸乙酯和正丁醇萃取部分异黄酮含量较高;氯仿、乙酸乙酯、正丁醇萃取物及水溶物4部分对DPPH自由基均有一定的清除作用,其中以乙酸乙酯萃取物的效果最佳;表明异黄酮是一种天然的抗氧化剂,具有较强的抗氧化作用.  相似文献   
2.
Syndecans, a family of transmembrane heparansulfate proteoglycans, are known to interact through their transmembrane domains to form non-covalently linked homodimers, a process essential for their individual functions. Because all syndecan transmembrane domains are highly conserved and thus might mediate interactions between different members of the syndecan family, we investigated syndecan interactions in detail. All recombinant syndecan-2 and -4 protein variants containing the transmembrane domain formed not only sodium dodecyl sulfate (SDS)-resistant homodimers but also SDS-resistant heterodimers. Biochemical and structural data revealed that recombinant syndecan-2 and -4 formed intermolecular interactions in vitro, and the GXXXG motif in transmembrane domain mediated this interaction. When exogenously expressed in rat embryonic fibroblasts, syndecan-2 interacted with syndecan-4 and vice versa. Furthermore, bimolecular fluorescence complementation-based assay demonstrated specific hetero-molecular interactions between syndecan-2 and -4, supporting hetero-oligomer formation of syndecans in vivo. Interestingly, hetero-oligomerization significantly reduced syndecan-4-mediated cellular processes such as protein kinase Cα activation and protein kinase Cα-mediated cell adhesion as well as syndecan-2-mediated tumorigenic activities in colon cancer cells such as migration and anchorage-independent growth. Taken together, these data provide evidence that hetero-oligomerization produces distinct syndecan functions and offer insights into the underlying signaling mechanisms of syndecans.  相似文献   
3.
The receptor for advanced glycation end products (RAGE) is a multi-ligand receptor of the immunoglobulin superfamily that has been implicated in multiple neuronal and inflammatory stress processes. In this study, we examined changes in RAGE immunoreactivity and its protein levels in the gerbil hippocampus (CA1-3 regions) after 5 min of transient global cerebral ischemia. The ischemic hippocampus was stained with cresyl violet, neuronal nuclei (a neuron-specific soluble nuclear antigen) antibody and Fluoro-Jade B (a marker for neuronal degeneration). 5 days after ischemia–reperfusion, delayed neuronal death occurred in the stratum pyramidale of the CA1 region. RAGE immunoreactivity was not detected in any regions of the CA1-3 regions of the sham-group; the immunoreactivity was markedly increased only in the CA1 region from 3 days after ischemia–reperfusion. On the other hand, RAGE immunoreactivity was newly expressed in astrocytes, not in microglia. Western blot analysis showed that RAGE protein level was highest at 5 days post-ischemia. In brief, both the RAGE immunoreactivity and protein level were distinctively increased in astrocytes in the ischemic CA1 region from 3 days after transient cerebral ischemia. These results indicate that the increase of RAGE expression in astrocytes after ischemia–reperfusion may be related to the ischemia-caused activation of astrocytes in the ischemic CA1 region.  相似文献   
4.
2-(Trimethylammonium) ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate [(R)-TEMOSPho], a derivative of an organic chemical identified from a natural product library, promotes highly efficient megakaryopoiesis. Here, we show that (R)-TEMOSPho blocks osteoclast maturation from progenitor cells of hematopoietic origin, as well as blocking the resorptive function of mature osteoclasts. The inhibitory effect of (R)-TEMOSPho on osteoclasts was due to a disruption of the actin cytoskeleton, resulting from impaired downstream signaling of c-Fms, a receptor for macrophage-colony stimulating factor linked to c-Cbl, phosphoinositol-3-kinase (PI3K), Vav3, and Rac1. In addition, (R)-TEMOSPho blocked inflammation-induced bone destruction by reducing the numbers of osteoclasts produced in mice. Thus, (R)-TEMOSPho may represent a promising new class of antiresorptive drugs for the treatment of bone loss associated with increased osteoclast maturation and activity.  相似文献   
5.
Mitochondrial dysfunction is implicated in age‐related degenerative disorders such as Alzheimer's disease (AD). Maintenance of mitochondrial dynamics is essential for regulating mitochondrial function. Aβ oligomers (AβOs), the typical cause of AD, lead to mitochondrial dysfunction and neuronal loss. AβOs have been shown to induce mitochondrial fragmentation, and their inhibition suppresses mitochondrial dysfunction and neuronal cell death. Oxidative stress is one of the earliest hallmarks of AD. Cyclin‐dependent kinase 5 (Cdk5) may cause oxidative stress by disrupting the antioxidant system, including Prx2. Cdk5 is also regarded as a modulator of mitochondrial fission; however, a precise mechanistic link between Cdk5 and mitochondrial dynamics is lacking. We estimated mitochondrial morphology and alterations in mitochondrial morphology‐related proteins in Neuro‐2a (N2a) cells stably expressing the Swedish mutation of amyloid precursor protein (APP), which is known to increase AβO production. We demonstrated that mitochondrial fragmentation by AβOs accompanies reduced mitofusin 1 and 2 (Mfn1/2) levels. Interestingly, the Cdk5 pathway, including phosphorylation of the Prx2‐related oxidative stress, has been shown to regulate Mfn1 and Mfn2 levels. Furthermore, Mfn2, but not Mfn1, over‐expression significantly inhibits the AβO‐mediated cell death pathway. Therefore, these results indicate that AβO‐mediated oxidative stress triggers mitochondrial fragmentation via decreased Mfn2 expression by activating Cdk5‐induced Prx2 phosphorylation.

  相似文献   

6.
Meta-analyses of European populations has successfully identified genetic variants in over 150 loci associated with lipid levels, but results from additional ethnicities remain limited. Previously, we reported two novel lipid loci identified in a sample of 7,657 African Americans using a gene-centric array including 50,000 SNPs in 2,100 candidate genes. Initial discovery and follow-up of signals with P < 10−5 in additional African American samples confirmed CD36 and ICAM1. Using an additional 8,244 African American female samples from the Women’s Health Initiative SNP Health Association Resource genome-wide association study dataset, we further examined the previous meta-analyses results by attempting to replicate 20 additional putative lipid signals with P < 10−4. Replication confirmed rs868213, located in a splice donor region of exocyst complex component 3-like 1 (EXOC3L1) as a novel signal for HDL (additive allelic effect β = 0.02; P = 1.4 × 10−8; meta-analyses of discovery and replication). EXOC3L1 is strongly expressed in vascular endothelium and forms part of the exocyst complex, a key facilitator of the trafficking of lipid receptors. Increasing sample sizes for genetic studies in nonEuropean populations will continue to improve our understanding of lipid metabolism.  相似文献   
7.
Sleep and Biological Rhythms - Neuroticism has been found to predispose individuals to depression, but the underlying mechanism is not well studied. The current study sought to delineate the...  相似文献   
8.
三倍体毛白杨叶片营养DRIS诊断   总被引:4,自引:0,他引:4  
采用L1645正交设计法对造林后的三倍体毛白杨进行了施肥试验,运用DRIS诊断法对其叶片营养元素进行了研究.结果表明,以造林第3年7~10月份三倍体毛白杨叶片N、P、K元素浓度测定值为依据,成功制定了DRIS图解法及指数法的营养诊断标准,经检验取得了较高的诊断正确率.三倍体毛白杨叶片N、P、K三元素浓度最佳比值范围为N/P=19.116±1.270;N/K=3.054±0.289;K/P=6.356±0.651.DRIS诊断标准分别经各月份林木叶片养分元素浓度回代检验,林木N、P、K需肥次序与实际施肥量基本一致,其中以9月份林木各处理为例,诊断正确率达到了80%以上.3年生三倍体毛白杨林木对N、P、K需求次序为N>K>P,与DRIS诊断结果一致.运用DRIS法诊断得到的三倍体毛白杨叶片养分浓度最佳比值范围将为三倍体毛白杨的合理施肥,大面积推广提供科学依据.  相似文献   
9.
Red soils, which are widely distributed in tropical and subtropical regions of southern China, are characterized by low organic carbon, high content of iron oxides, and acidity and, hence, are likely to be ideal habitats for acidophilic actinomycetes. However, the diversity and biosynthetic potential of actinomycetes in such habitats are underexplored. Here, a total of 600 actinomycete strains were isolated from red soils collected in Jiangxi Province in southeast China. 16S rRNA gene sequence analysis revealed a high diversity of the isolates, which were distributed into 26 genera, 10 families, and 7 orders within the class Actinobacteria; these taxa contained at least 49 phylotypes that are likely to represent new species within 15 genera. The isolates showed good physiological potentials for biosynthesis and biocontrol. Chemical screening of 107 semirandomly selected isolates spanning 20 genera revealed the presence of at least 193 secondary metabolites from 52 isolates, of which 125 compounds from 39 isolates of 12 genera were putatively novel. Macrolides, polyethers, diketopiperazines, and siderophores accounted for most of the known compounds. The structures of six novel compounds were elucidated, two of which had a unique skeleton and represented characteristic secondary metabolites of a putative novel Streptomyces phylotype. These results demonstrate that red soils are rich reservoirs for diverse culturable actinomycetes, notably members of the families Streptomycetaceae, Pseudonocardiaceae, and Streptosporangiaceae, with the capacity to synthesize novel bioactive compounds.  相似文献   
10.
UDP‐glucuronosyltransferases (UGTs)‐catalyzed glucuronidation conjugation reaction plays an important role in the elimination of many important clinical drugs and endogenous substances. The present study aims to investigate the enantioselective inhibition of carprofen towards UGT isoforms. In vitro a recombinant UGT isoforms‐catalyzed 4‐methylumbelliferone (4‐MU) glucuronidation incubation mixture was used to screen the inhibition potential of (R)‐carprofen and (S)‐carprofen towards multiple UGT isoforms. The results showed that (S)‐carprofen exhibited stronger inhibition potential than (R)‐carprofen towards UGT2B7. However, no significant difference was observed for the inhibition of (R)‐carprofen and (S)‐carprofen towards other UGT isoforms. Furthermore, the inhibition kinetic behavior was compared for the inhibition of (S)‐carprofen and (R)‐carprofen towards UGT2B7. A Lineweaver–Burk plot showed that both (S)‐carprofen and (R)‐carprofen exhibited competitive inhibition towards UGT2B7‐catalyzed 4‐MU glucuronidation. The inhibition kinetic parameter (Ki) was calculated to be 7.0 μM and 31.1 μM for (S)‐carprofen and (R)‐carprofen, respectively. Based on the standard for drug–drug interaction, the threshold for (S)‐carprofen and (R)‐carprofen to induce a drug–drug interaction is 0.7 μM and 3.1 μM, respectively. In conclusion, enantioselective inhibition of carprofen towards UDP‐glucuronosyltransferase (UGT) 2B7 was demonstrated in the present study. Using the in vitro inhibition kinetic parameter, the concentration threshold of (S)‐carprofen and (R)‐carprofen to possibly induce the drug–drug interaction was obtained. Therefore, clinical monitoring of the plasma concentration of (S)‐carprofen is more important than (R)‐carprofen to avoid a possible drug–drug interaction between carprofen and the drugs mainly undergoing UGT2B7‐catalyzed metabolism. Chirality 27:189–193, 2015. © 2014 Wiley Periodicals, Inc.  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