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   3795篇
  免费   340篇
  国内免费   325篇
  2024年   7篇
  2023年   45篇
  2022年   111篇
  2021年   201篇
  2020年   131篇
  2019年   165篇
  2018年   155篇
  2017年   123篇
  2016年   184篇
  2015年   224篇
  2014年   248篇
  2013年   280篇
  2012年   320篇
  2011年   289篇
  2010年   185篇
  2009年   165篇
  2008年   205篇
  2007年   154篇
  2006年   167篇
  2005年   145篇
  2004年   136篇
  2003年   107篇
  2002年   115篇
  2001年   97篇
  2000年   85篇
  1999年   79篇
  1998年   46篇
  1997年   44篇
  1996年   38篇
  1995年   34篇
  1994年   28篇
  1993年   21篇
  1992年   19篇
  1991年   23篇
  1990年   11篇
  1989年   6篇
  1988年   10篇
  1987年   14篇
  1986年   8篇
  1985年   8篇
  1984年   8篇
  1983年   4篇
  1982年   2篇
  1981年   5篇
  1980年   1篇
  1979年   2篇
  1978年   2篇
  1977年   1篇
  1974年   1篇
  1971年   1篇
排序方式: 共有4460条查询结果,搜索用时 30 毫秒
901.
Evidence indicates that stress conditions might lead to drug dependence. Recently, we have demonstrated that exposure to far infrared ray (FIR) attenuates acute restraint stress via induction of glutathione peroxidase-1 (GPx-1) gene. We investigated whether FIR affects methamphetamine (MA)-induced behavioral sensitization and whether FIR-mediated pharmacological activity requires interaction between dopamine receptor and GPx-1 gene. We observed that MA treatment significantly increased GPx-1 expression in the striatum of wild-type (WT) mice. Interestingly, exposure to FIR potentiated MA-induced increase in GPx-1 expression. This phenomenon was also observed in animals receiving MA with dopamine D1 receptor antagonist SCH23390. However, dopamine D2 receptor antagonist sulpiride did not affect MA-induced GPx-1 expression. FIR exposure or SCH23390, but not sulpiride, significantly attenuated MA-induced behavioral sensitization. Exposure to FIR significantly attenuated MA-induced dopamine D1 receptor expression, c-Fos induction and oxidative burdens. FIR-mediated antioxidant effects were also more pronounced in mitochondrial- than cytosolic-fraction. In addition, FIR significantly attenuated against MA-induced changes in mitochondrial superoxide dismutase and mitochondrial GPx activities, mitochondrial transmembrane potential, intramitochondrial Ca2+ level, mitochondrial complex-I activity, and mitochondrial oxidative burdens. The attenuation by FIR was paralleled that by SCH23390. Effects of FIR or SCH23390 were more sensitive to GPx-1 KO than WT mice, while SCH23390 treatment did not exhibit any additive effects on the protective activity mediated by FIR, indicating that dopamine D1 receptor constitutes a molecular target of FIR. Our result suggests that exposure to FIR ameliorates MA-induced behavioral sensitization via possible interaction between dopamine D1 receptor and GPx-1 gene.  相似文献   
902.
The purpose of this meta‐analysis was to comprehensively investigate the correlation between high mobility group box 1 (HMGB1) and interleukin‐6 (IL‐6) in relation to acute pancreatitis. A highly regulated exploration of various electronic databases, supplemented by manual searching methods, was performed in an attempt to identify pertinent articles of a useful nature. Subsequently, high‐quality cohort studies that were deemed to comply with the arduous inclusion and exclusion criteria were selected for our meta‐analysis. The extensive data analyses reported in our meta‐analysis were conducted in connection with the Comprehensive Meta‐analysis 2.0 (CMA 2.0). A total of 395 studies (135 Chinese studies and 260 English studies) were initially retrieved. 27 of those studies were selected for our meta‐analysis, comprising of 896 cases of mild acute pancreatitis (MAP), 700 cases of severe acute pancreatitis (SAP) as well as 312 healthy controls. Pooled data suggested that serum HMGB1 and IL‐6 levels of SAP and MAP patients were higher than in healthy controls. Moreover, serum HMGB1 and IL‐6 levels of SAP patients exhibited significantly higher levels than in that of MAP patients. Based on the rigorous investigation of our meta‐analysis, it was concluded that serum HMGB1 and IL‐6 levels might be used as effective indicators for pancreatic lesions as well as the degree of inflammatory response, owing ultimately to the observations and data analyses, suggesting that serum HMGB1 and IL‐6 levels share a close correlation with the severity of pancreatitis. J. Cell. Biochem. 119: 616–624, 2018. © 2017 Wiley Periodicals, Inc.  相似文献   
903.
ICAM3 was reported to promote metastasis in tumors. However, the underlying mechanism remains elusive. Here, we disclosed that the expression of ICAM3 was closely correlated with the TNM stage of human breast and lung cancer, as well as the dominant overexpression in high aggressive tumor cell lines (231 and A549 cells). Moreover, the knockdown of ICAM3 inhibited tumor metastasis whereas the ectopic expression of ICAM3 promoted tumor metastasis both in vitro and in vivo. In addition, exploration of the underlying mechanism demonstrated that ICAM3 not only binds to LFA-1 with its extracellular domain and structure protein ERM but also to lamellipodia with its intracellular domain which causes a tension that pulls cells apart (metastasis). Furthermore, ICAM3 extracellular or intracellular mutants alternatively abolished ICAM3 mediated tumor metastasis in vitro and in vivo. As a therapy strategy, LFA-1 antibody or Lifitegrast restrained tumor metastasis via targeting ICAM3-LFA-1 interaction. In summary, the aforementioned findings suggest a model of ICAM3 in mediating tumor metastasis. This may provide a promising target or strategy for the prevention of tumor metastasis.  相似文献   
904.
Circular dichroism (CD) spectroscopy is a widely used technique for the evaluation of protein secondary structures that has a significant impact for the understanding of molecular biology. However, the quantitative analysis of protein secondary structures based on CD spectra is still a hard work due to the serious overlap of the spectra corresponding to different structural motifs. Here, Tchebichef image moment (TM) approach is introduced for the first time, which can effectively extract the chemical features in CD spectra for the quantitative analysis of protein secondary structures. The proposed approach was applied to analyze reference set and the obtained results were evaluated by the strict statistical parameters such as correlation coefficient, cross‐validation correlation coefficient and root mean squared error. Compared with several specialized prediction methods, TM approach provided satisfactory results, especially for turns and unordered structures. Our study indicates that TM approach can be regarded as a feasible tool for the analysis of the secondary structures of proteins based on CD spectra. An available TMs package is provided and can be used directly for secondary structures prediction.  相似文献   
905.
林业剩余物资源量评估方法   总被引:1,自引:0,他引:1  
根据近十年来相关文献报道,分析了前人所建方法的合理性,结合中国林业生产实际,完善了林业剩余物资源潜力的计算方法。主要贡献包括:林业剩余物第二级分类的10个主要类型,即林木苗圃剩余物、林木修枝剩余物、木材采伐剩余物、木材造材剩余物、木材加工剩余物、竹材加工剩余物、薪材、废旧竹材、废旧木材、香蕉和菠萝残体;将经济林采伐和进口原木产生的剩余物计入相关木材剩余物计算范围;首次建立了包括木本水果在内的林木修枝剩余物的计算方法,以及多年生草本水果剩余物即香蕉和菠萝残体产量的计算方法;确定计算公式中参数所需要数据的来源;建议今后重点研究相关系数取值、林业剩余物资源量及其空间分布和相关行业标准等。  相似文献   
906.
Multi‐parent advanced generation inter‐cross (MAGIC) populations are an emerging type of resource for dissecting the genetic structure of traits and improving breeding populations. We developed a MAGIC population for cowpea (Vigna unguiculata L. Walp.) from eight founder parents. These founders were genetically diverse and carried many abiotic and biotic stress resistance, seed quality and agronomic traits relevant to cowpea improvement in the United States and sub‐Saharan Africa, where cowpea is vitally important in the human diet and local economies. The eight parents were inter‐crossed using structured matings to ensure that the population would have balanced representation from each parent, followed by single‐seed descent, resulting in 305 F8 recombinant inbred lines each carrying a mosaic of genome blocks contributed by all founders. This was confirmed by single nucleotide polymorphism genotyping with the Illumina Cowpea Consortium Array. These lines were on average 99.74% homozygous but also diverse in agronomic traits across environments. Quantitative trait loci (QTLs) were identified for several parental traits. Loci with major effects on photoperiod sensitivity and seed size were also verified by biparental genetic mapping. The recombination events were concentrated in telomeric regions. Due to its broad genetic base, this cowpea MAGIC population promises breakthroughs in genetic gain, QTL and gene discovery, enhancement of breeding populations and, for some lines, direct releases as new varieties.  相似文献   
907.
908.
The design and synthesis of a novel series of 2,6-disubstituted pyrazine derivatives as CK2 kinase inhibitors is described. Structure-guided optimization of a 5-substituted-3-thiophene carboxylic acid screening hit (3a) led to the development of a lead compound (12b), which shows inhibition in both enzymatic and cellular assays. Subsequent design and hybridization efforts also led to the unexpected identification of analogs with potent PIM kinase activity (14f).  相似文献   
909.
910.
Bao  Hong-duo  Pang  Mao-da  Olaniran  Ademola  Zhang  Xu-hui  Zhang  Hui  Zhou  Yan  Sun  Li-chang  Schmidt  Stefan  Wang  Ran 《Applied microbiology and biotechnology》2018,102(23):10219-10230

Phages, the most abundant species in the mammalian gut, have numerous advantages as biocontrol agent over antibiotics. In this study, mice were orally treated with the lytic gut phage PA13076 (group B), the temperate phage BP96115 (group C), no phage (group A), or streptomycin (group D) over 31 days. At the end of the experiment, fecal microbiota diversity and composition was determined and compared using high-throughput sequencing of the V3–V4 hyper-variable region of the 16S rRNA gene and virus-like particles (VLPs) were quantified in feces. There was high diversity and richness of microbiota in the lytic and temperate gut phage-treated mice, with the lytic gut phage causing an increased alpha diversity based on the Chao1 index (p < 0.01). However, the streptomycin treatment reduced the microbiota diversity and richness (p = 0.0299). Both phage and streptomycin treatments reduced the abundance of Bacteroidetes at the phylum level (p < 0.01) and increased the abundance of the phylum Firmicutes. Interestingly, two beneficial genera, Lactobacillus and Bifidobacterium, were enhanced by treatment with the lytic and temperate gut phage. The abundance of the genus Escherichia/Shigella was higher in mice after temperate phage administration than in the control group (p < 0.01), but lower than in the streptomycin group. Moreover, streptomycin treatment increased the abundance of the genera Klebsiella and Escherichia/Shigella (p < 0.01). In terms of the gut virome, fecal VLPs did not change significantly after phage treatment. This study showed that lytic and temperate gut phage treatment modulated the composition and diversity of gut microbiota and the lytic gut phage promoted a beneficial gut ecosystem, while the temperate phage may promote conditions enabling diseases to occur.

  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