全文获取类型
收费全文 | 5460篇 |
免费 | 406篇 |
国内免费 | 280篇 |
专业分类
6146篇 |
出版年
2024年 | 8篇 |
2023年 | 76篇 |
2022年 | 132篇 |
2021年 | 245篇 |
2020年 | 190篇 |
2019年 | 232篇 |
2018年 | 204篇 |
2017年 | 182篇 |
2016年 | 289篇 |
2015年 | 335篇 |
2014年 | 379篇 |
2013年 | 431篇 |
2012年 | 503篇 |
2011年 | 442篇 |
2010年 | 268篇 |
2009年 | 209篇 |
2008年 | 286篇 |
2007年 | 231篇 |
2006年 | 204篇 |
2005年 | 180篇 |
2004年 | 189篇 |
2003年 | 136篇 |
2002年 | 145篇 |
2001年 | 82篇 |
2000年 | 51篇 |
1999年 | 75篇 |
1998年 | 51篇 |
1997年 | 56篇 |
1996年 | 41篇 |
1995年 | 31篇 |
1994年 | 34篇 |
1993年 | 21篇 |
1992年 | 33篇 |
1991年 | 14篇 |
1990年 | 13篇 |
1989年 | 15篇 |
1988年 | 15篇 |
1987年 | 13篇 |
1986年 | 10篇 |
1985年 | 11篇 |
1984年 | 12篇 |
1983年 | 19篇 |
1980年 | 5篇 |
1979年 | 6篇 |
1978年 | 5篇 |
1977年 | 5篇 |
1975年 | 6篇 |
1974年 | 5篇 |
1973年 | 6篇 |
1970年 | 3篇 |
排序方式: 共有6146条查询结果,搜索用时 15 毫秒
31.
Hanxing Wan Xiong Ying Chen Fenglian Zhang Jun Chen Fenglan Chu Zachary M. Sellers Feng Xu Hui Dong 《The Journal of biological chemistry》2022,298(5)
Although capsaicin has been studied extensively as an activator of the transient receptor potential vanilloid cation channel subtype 1 (TRPV1) channels in sensory neurons, little is known about its TRPV1-independent actions in gastrointestinal health and disease. Here, we aimed to investigate the pharmacological actions of capsaicin as a food additive and medication on intestinal ion transporters in mouse models of ulcerative colitis (UC). The short-circuit current (Isc) of the intestine from WT, TRPV1-, and TRPV4-KO mice were measured in Ussing chambers, and Ca2+ imaging was performed on small intestinal epithelial cells. We also performed Western blots, immunohistochemistry, and immunofluorescence on intestinal epithelial cells and on intestinal tissues following UC induction with dextran sodium sulfate. We found that capsaicin did not affect basal intestinal Isc but significantly inhibited carbachol- and caffeine-induced intestinal Isc in WT mice. Capsaicin similarly inhibited the intestinal Isc in TRPV1 KO mice, but this inhibition was absent in TRPV4 KO mice. We also determined that Ca2+ influx via TRPV4 was required for cholinergic signaling–mediated intestinal anion secretion, which was inhibited by capsaicin. Moreover, the glucose-induced jejunal Iscvia Na+/glucose cotransporter was suppressed by TRPV4 activation, which could be relieved by capsaicin. Capsaicin also stimulated ouabain- and amiloride-sensitive colonic Isc. Finally, we found that dietary capsaicin ameliorated the UC phenotype, suppressed hyperaction of TRPV4 channels, and rescued the reduced ouabain- and amiloride-sensitive Isc. We therefore conclude that capsaicin inhibits intestinal Cl- secretion and promotes Na+ absorption predominantly by blocking TRPV4 channels to exert its beneficial anti-colitic action. 相似文献
32.
Guo Zhao Xiaobing Gu Xinlun Lu Jinjin Pan Zhiqiang Duan Kunkun Zhao Min Gu Qingtao Liu Liang He Jian Chen Shengqiang Ge Yanhong Wang Sujuan Chen Xiaoquan Wang Daxin Peng Hongquan Wan Xiufan Liu 《PloS one》2012,7(9)
There has been multiple evidence that domestic poultry may act as a vessel for the generation of novel influenza A viruses. In this study, we have analyzed the evolution and pathogenicity of 4 H5N2 avian influenza viruses isolated from apparently healthy poultry from H5N1 virus endemic areas in China. Phylogenetic analysis revealed that two of these viruses, A/duck/Eastern China/1111/2011 (DK/EC/1111/11) and A/goose/Eastern China/1112/2011 (GS/EC/1112/11) were derived from reassortment events in which clade 2.3.4 highly pathogenic avian influenza (HPAI) H5N1 viruses acquired novel neuraminidase and nonstructural protein genes. Another two isolates, A/chicken/Hebei/1102/2010 (CK/HB/1102/10) and A/duck/Hebei/0908/2009 (DK/HB/0908/09), possess hemagglutinin (HA) gene belong to clade 7 H5 viruses and other genes from endemic H9N2 viruses, or from viruses of various subtypes of the natural gene pool. All of these H5N2 isolates bear characteristic sequences of HPAI virus at the cleavage site of HA, and animal experiments indicated that all of these viruses but DK/HB/0908/09 is highly pathogenic to chickens. In particular, DK/EC/1111/11 and GS/EC/1112/11 are also highly pathogenic to ducks and moderately pathogenic to mice. All of these 4 viruses were able to replicate in domestic ducks and mice without prior adaptation. The emergence of these novel H5N2 viruses adds more evidence for the active evolution of H5 viruses in Asia. The maintenance of the highly pathogenic phenotype of some of these viruses even after reassortment with a new NA subtypes, their ability to replicate and transmit in domestic poultry, and the pathogenicity in the mammalian mouse model, highlight the potential threat posed by these viruses to both veterinary and public health. 相似文献
33.
Xiangxiang Shan Yufeng Miao Rengen Fan Changzhi Song Guangzhou Wu Zhengqiang Wan Jian Zhu Guan Sun Wenzhang Zha Xiangming Mu Guangjun Zhou Yan Chen 《In vitro cellular & developmental biology. Animal》2013,49(8):576-582
In this study, we aimed to study the role of growth factor receptor-bound protein 2 (Grb2) in palmitic acid-induced steatosis and other “fatty liver” symptoms in vitro. HepG2 cells, with or without stably suppressed Grb2 expression, were incubated with palmitic acid for 24 h to induce typical clinical “fatty liver” features, including steatosis, impaired glucose metabolism, oxidative stress, and apoptosis. MTT and Oil Red O assays were applied to test cell viability and fat deposition, respectively. Glucose uptake assay was used to evaluate the glucose utilization of cells. Quantitative polymerase chain reaction and Western blot were used to measure expressional changes of key markers of insulin signaling, lipid/glucose metabolism, oxidative stress, and apoptosis. After 24-h palmitic acid induction, increased fat accumulation, reduced glucose uptake, impaired insulin signaling, enhanced oxidative stress, and increased apoptosis were observed in HepG2 cells. Suppression of Grb2 in HepG2 significantly reduced fat accumulation, improved glucose metabolism, ameliorated oxidative stress, and restored the activity of insulin receptor substrate-1/Akt and MEK/ERK pathways. In addition, Grb2 deficiency attenuated hepatic apoptosis shown by reduced activation of caspase-3 and fluorescent staining. Modulation of Bcl-2 and Bak1 also contributed to reduced apoptosis. In conclusion, suppression of Grb2 expression in HepG2 cells improved hepatic steatosis, glucose metabolism, oxidative stress, and apoptosis induced by palmitic acid incubation partly though modulating the insulin signaling pathway. 相似文献
34.
Lei Wang Jie Zheng Yanzhong Luo Tao Xu Qiuxue Zhang Lan Zhang Miaoyun Xu Jianmin Wan Ming‐Bo Wang Chunyi Zhang Yunliu Fan 《Plant biotechnology journal》2013,11(8):997-1005
Long hairpin RNA (hpRNA) transgenes are a powerful tool for gene function studies in plants, but a genomewide RNAi mutant library using hpRNA transgenes has not been reported for plants. Here, we report the construction of a hpRNA library for the genomewide identification of gene function in rice using an improved rolling circle amplification‐mediated hpRNA (RMHR) method. Transformation of rice with the library resulted in thousands of transgenic lines containing hpRNAs targeting genes of various function. The target mRNA was down‐regulated in the hpRNA lines, and this was correlated with the accumulation of siRNAs corresponding to the double‐stranded arms of the hpRNA. Multiple members of a gene family were simultaneously silenced by hpRNAs derived from a single member, but the degree of such cross‐silencing depended on the level of sequence homology between the members as well as the abundance of matching siRNAs. The silencing of key genes tended to cause a severe phenotype, but these transgenic lines usually survived in the field long enough for phenotypic and molecular analyses to be conducted. Deep sequencing analysis of small RNAs showed that the hpRNA‐derived siRNAs were characteristic of Argonaute‐binding small RNAs. Our results indicate that RNAi mutant library is a high‐efficient approach for genomewide gene identification in plants. 相似文献
35.
以氯代苯胺(PCA)为选择基质,用驯化技术从降解对二氯苯(p-DCB)的富集培养物中得到了以同化PCA为唯一碳源和氮源的混合微生物。将这种固定在填充床反应器中的微生物用于PCA的降解作用研究中。在该反应器里,PCA的生物降解遵循Logistic方程q=qmax/(1+eα-βUv).由方程求出了主要的动力学常数,Ks(半速率常数)和qmax(最大比基质降解速率).于PCA降解的同时,释放氯离子到培养基中。在水力停留时间3h, 进水PCA浓度为360mg·L-1情况下,基质的体积降解率达到125mg·L-1·h-1;基质的百分去除率为91%. 相似文献
36.
Faxiang Wan Yu Pan Jinghua Li Xiangfu Chen Yanglu Pan Yongqing Wang Shibing Tian Xingguo Zhang 《Plant cell reports》2014,33(12):1951-1961
Key message
Our study shows that the expression of AtCBF3 and AtCOR15A improved the chilling tolerance in transgenic eggplant.Abstract
In an attempt to improve chilling tolerance of eggplant (Solanum melongena L) plants, Arabidopsis C-repeat binding factor 3 (AtCBF3) and cold-regulated 15A (AtCOR15A) genes both driven by an Arabidopsis RESPONSIVE TO DESSICATION 29A promoter (AtRD29A) were transferred into the plants of eggplant cultivar Sanyueqie. Two independent homozygous transgenic lines were tested for their cold tolerance. The leaves of the transgenic plants in both lines withered much slower and slighter than the wild-type plants after exposure to cold stress treatment at 2 ± 1 °C. The gene expression of AtCBF3 and AtCOR15A was significantly increased as well as the proline content and the levels of catalase and peroxidase activities, while the relative electrical conductivity and the malondialdehyde content were remarkably decreased in the transgenic plants compared with the wild type at 4 ± 0.5 °C. The results showed that the expression of the exogenous AtCBF3 and AtCOR15A could promote the cold adaptation process to protect eggplant plants from chilling stress. 相似文献37.
38.
Zhao G Wan W Mansouri S Alfaro JF Bassler BL Cornell KA Zhou ZS 《Bioorganic & medicinal chemistry letters》2003,13(22):3897-3900
Bacterial quorum sensing is mediated by autoinducers, small signaling molecules generated by bacteria. It has been proposed that the LuxS enzyme converts S-ribosyl-L-homocysteine to 4,5-dihydroxy-2,3-pentanedione, the precursor of autoinducer 2 (AI-2). We report here a chemical synthesis of S-ribosyl-L-homocysteine and its analogue using Mitsunobu coupling. Chemically synthesized ribosylhomocysteine has been confirmed as a substrate for LuxS in both an enzyme assay and a whole cell quorum sensing assay. The chemical entities of products from the LuxS reaction were also established. Several ribosylhomocysteine analogues have been tested as LuxS inhibitors. 相似文献
39.
Zhang Hao Wang Jin-Yan Chen Yi-Juan Siemann Evan Ji Xiang-Yun Jiang Jie-Xian Wan Nian-Feng 《BioControl》2022,67(1):1-13
BioControl - The effects of plant volatiles on parasitoids are important with regards to the tri-trophic interactions among host plants, insect herbivores, and their natural enemies. However, the... 相似文献