全文获取类型
收费全文 | 11336篇 |
免费 | 910篇 |
国内免费 | 758篇 |
专业分类
13004篇 |
出版年
2024年 | 20篇 |
2023年 | 212篇 |
2022年 | 395篇 |
2021年 | 629篇 |
2020年 | 395篇 |
2019年 | 512篇 |
2018年 | 535篇 |
2017年 | 341篇 |
2016年 | 508篇 |
2015年 | 710篇 |
2014年 | 791篇 |
2013年 | 915篇 |
2012年 | 1067篇 |
2011年 | 928篇 |
2010年 | 571篇 |
2009年 | 495篇 |
2008年 | 533篇 |
2007年 | 492篇 |
2006年 | 427篇 |
2005年 | 361篇 |
2004年 | 302篇 |
2003年 | 225篇 |
2002年 | 187篇 |
2001年 | 202篇 |
2000年 | 170篇 |
1999年 | 174篇 |
1998年 | 101篇 |
1997年 | 123篇 |
1996年 | 105篇 |
1995年 | 87篇 |
1994年 | 91篇 |
1993年 | 48篇 |
1992年 | 74篇 |
1991年 | 55篇 |
1990年 | 44篇 |
1989年 | 46篇 |
1988年 | 38篇 |
1987年 | 27篇 |
1986年 | 19篇 |
1985年 | 22篇 |
1984年 | 12篇 |
1983年 | 9篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1979年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
191.
Xi Chen Fang Lu Ganggang Luo Yue Ren Jing Ma 《Journal of biomolecular structure & dynamics》2020,38(15):4461-4470
AbstractFarnesoid X receptor (FXR), a bile acid receptor, has important roles in maintaining bile acid and cholesterol homeostasis, which is an attractive target for hyperlipidemia. Present study aimed to discover potential selective FXR agonists over G-protein coupled bile acid receptor 1 (GPBAR1, TGR5) from traditional Chinese medicine (TCM) by using virtual screening, in vitro studies and molecular dynamics simulation (MD). Ligand-based pharmacophore model for FXR was firstly built to screen FXR agonists from the Traditional Chinese Medicine Database (TCMD). Then, 21 FXR crystal structures were clustered in two types and two representative structures (PDB ID: 3OMM and 3P89) were, respectively, used to carry out molecular docking to refine the screened result. Moreover, the pharmacophore model for GPBAR1 was built to screen selective FXR agonists with no activity on GPBAR1. A set of 24 candidate selective FXR agonists which fitvalue of FXR pharmacophore model and docking score of 3OMM and 3P89 were in the top 100 and cannot match the pharmacophore model for GPBAR1 were obtained. By the lipid-lowering activity test in HepG2 cell lines, Arctigenin was identified to be potential selective FXR agonist with the activity of 20?μmol·L?1. After down-regulating FXR, Arctigenin could increase the mRNA of FXR while exerted no effect on the mRNA of GPBAR1. MD was further used to interpret the mechanism of Arctigenin with the representative structures. This research provided a new screening procedure for finding selective candidate compounds and appropriate docking models of a target by considering the structure diversity of PDB structures, which was applied to discovery novel selective FXR agonists to treat hyperlipidemia.Communicated by Ramaswamy H. Sarma 相似文献
192.
Lu Haotian Shi Chunying Wang Shuang Yang Chaochao Wan Xueqi Luo Yunzhe Tian Le Li Ling 《Molecular biology reports》2020,47(10):7831-7842
Molecular Biology Reports - Non-SMC condensin I complex subunit H (NCAPH) is a structural component of chromosomes during mitosis, which up-regulates in various cancers. However, the role of NCAPH... 相似文献
193.
Xiao Xiao Bai Peng Cao Shuqiang Jiang Youjing Liang Weibo Wang Tao Luo Xiaolei Guan Qiaozhi Gao Linbo Zhang Lin 《Neurochemical research》2020,45(4):928-939
Neurochemical Research - High-throughput and bioinformatics technology have been broadly applied to demonstrate the key molecules involved in traumatic brain injury (TBI), while no study has... 相似文献
194.
Evan Wells Liqing Song Madison Greer Yu Luo Varghese Kurian Babatunde Ogunnaike Anne S. Robinson 《Biotechnology and bioengineering》2020,117(11):3310-3321
Monoclonal antibodies are critically important biologics as the largest class of molecules used to treat cancers, rheumatoid arthritis, and other chronic diseases. Antibody glycosylation is a critical quality attribute that has ramifications for patient safety and physiological efficacy—one that can be modified by such factors as media formulation and process conditions during production. Using a design-of-experiments approach, we examined the effect of 2-F-peracetyl fucose (2FP), uridine, and galactose on cell growth and metabolism, titer, and gene expression of key glycosylation-related proteins, and report how the glycoform distribution changed from Days 4 to 7 in a batch process used for IgG1 production from Chinese hamster ovary cells. We observed major glycosylation changes upon supplement addition, where the addition of 2FP decreased antibody fucosylation by up to 48%, galactose addition increased galactosylation by up to 21%, and uridine addition decreased fucosylation and increased galactosylation by 6% and 2%, respectively. Despite having major effects on glycosylation, neither galactose nor 2FP significantly affected cell culture growth, metabolism, or titer. Uridine improved peak cell densities by 23% but also reduced titer by ∼30%. The supplements caused significant changes in gene expression by Day 4 of the cultures where 2FP addition significantly reduced fucosyltransferase 8 and nucleotide sugar transporter gene expression (by ∼2-fold), and uridine addition significantly increased expression of UDP-GlcNAcT (SLC35A3) and B4GALT1–6 genes (by 1.5–3-fold). These gene expression data alongside glycosylation, metabolic, and growth data improve our understanding of the cellular mechanisms affected by media supplementation and suggest approaches for modifying antibody glycosylation in antibody production processes. 相似文献
195.
196.
197.
Haiyan Chu Qinghong Zhao Shizhi Wang Meilin Wang Ming Xu Yan Gao Dewei Luo Yongfei Tan Weida Gong Zhengdong Zhang Dongmei Wu 《Gene》2013
ERCC4 plays an essential role in the nucleotide excision repair (NER) pathway, which is involved in the removal of a wide variety of DNA lesions. To determine whether the ERCC4 tagging SNPs (tSNPs) are associated with risk of gastric cancer, we conducted a hospital-based case-control study of 350 cases and 468 cancer-free controls. In the logistic regression (LR) analysis, we found a significantly decreased risk of gastric cancer associated with the rs744154 GC/CC genotypes [adjusted odds ratio (OR) = 0.56, 95% confidence interval (CI) = 0.42–0.75, false discovery rate (FDR) P = 0.003] compared with the wild-type GG genotype. Haplotype-based association study revealed that the CGC haplotype that containing the rs744154 C allele can decrease the risk of gastric cancer compared with the most common haplotype GGT (adjusted OR = 0.61, 95% CI = 0.46–0.81). Using the multifactor dimensionality reduction (MDR) analysis, we identified that the SNP rs744154 and smoking status were the best two predictive factors for gastric cancer with a testing accuracy of 55.76% and a perfect cross-validation consistency (CVC) of 10 (P = 0.001). Furthermore, the smokers with the rs744154 GC/CC genotypes showed a decreased risk of gastric cancer (adjusted OR = 0.55, 95% CI = 0.35–0.85) compared with the smokers with the GG genotype using multivariate LR analysis. The above findings consistently suggested that genetic variants in the ERCC4 gene may play a protective role in the etiology of gastric cancer, even in the smokers. 相似文献
198.
Jipeng Li Yulan Song Yiping Wang Jianping Luo Wanjun Yu 《Molecular and cellular biochemistry》2013,380(1-2):277-282
Recent studies have implied that miRNAs act as crucial modulators for epithelial-to-mesenchymal transition (EMT). We found that miR-148a is significantly downregulated in non-small cell lung cancer (NSCLC) compared to adjacent non-cancerous lung tissues, and the downregulated miR-148a was significantly associated with lymph-node metastasis. Functional assays demonstrated that miR-148a inhibited EMT in NSCLC cells. Moreover, miR-148a decreased 3′-untranslated region luciferase activity of ROCK1 and ROCK1 protein expression. Knockdown of ROCK1 reversed EMT resembling that of miR-148a overexpression. Furthermore, ROCK1 was widely upregulated in NSCLC, and its mRNA levels were inversely correlated with miR-148a expression. These findings suggest that miR-148a acts as a novel EMT suppressor in NSCLC cells, at least in part by modulation of ROCK1. 相似文献
199.
200.
L. H. Wu Y. J. Liu S. B. Zhou F. G. Guo D. Bi X. H. Guo A. J. M. Baker J. A. C. Smith Y. M. Luo 《Plant Systematics and Evolution》2013,299(3):487-498
Sedum plumbizincicola X.H. Guo et S.B. Zhou ex L.H. Wu (Crassulaceae), a new species restricted to lead–zinc mining areas in Zhejiang Province, China, is described and illustrated. This taxon belongs to sect. Sedum (H. Ohba) S.H. Fu based on the adaxially gibbous carpels and follicles. It superficially resembles S. alfredii Hance and three other Sedum species found in the same area, but differs from these other taxa in bearing 4-merous flowers. Differences in geographical distribution, growth habit, phenology, macromorphology, leaf and stem anatomy, as well as seed micromorphology among S. plumbizincicola, S. alfredii and other related taxa in the genus Sedum are also reported. nrDNA internal transcribed spacers (ITS) sequences from seven populations of S. plumbizincicola support the recognition of this as a taxonomic entity distinct from S. alfredii. 相似文献