全文获取类型
收费全文 | 10181篇 |
免费 | 1523篇 |
国内免费 | 2089篇 |
出版年
2024年 | 8篇 |
2023年 | 242篇 |
2022年 | 314篇 |
2021年 | 384篇 |
2020年 | 594篇 |
2019年 | 799篇 |
2018年 | 667篇 |
2017年 | 578篇 |
2016年 | 602篇 |
2015年 | 538篇 |
2014年 | 702篇 |
2013年 | 828篇 |
2012年 | 548篇 |
2011年 | 615篇 |
2010年 | 518篇 |
2009年 | 559篇 |
2008年 | 565篇 |
2007年 | 552篇 |
2006年 | 533篇 |
2005年 | 472篇 |
2004年 | 392篇 |
2003年 | 353篇 |
2002年 | 309篇 |
2001年 | 238篇 |
2000年 | 245篇 |
1999年 | 181篇 |
1998年 | 137篇 |
1997年 | 108篇 |
1996年 | 94篇 |
1995年 | 129篇 |
1994年 | 108篇 |
1993年 | 89篇 |
1992年 | 82篇 |
1991年 | 63篇 |
1990年 | 35篇 |
1989年 | 39篇 |
1988年 | 33篇 |
1987年 | 31篇 |
1986年 | 35篇 |
1985年 | 50篇 |
1984年 | 111篇 |
1983年 | 60篇 |
1982年 | 76篇 |
1981年 | 52篇 |
1980年 | 38篇 |
1979年 | 37篇 |
1978年 | 25篇 |
1977年 | 6篇 |
1976年 | 7篇 |
1975年 | 8篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
51.
《Bioorganic & medicinal chemistry》2020,28(11):115492
Effective chemotherapy for solid cancers is challenging due to a limitation in permeation that prevents anticancer drugs from reaching the center of the tumor, therefore unable to limit cancer cell growth. To circumvent this issue, we planned to apply the drugs directly at the center by first collapsing the outer structure. For this, we focused on cell–cell communication (CCC) between N-glycans and proteins at the tumor cell surface. Mature N-glycans establish CCC; however, CCC is hindered when numerous immature N-glycans are present at the cell surface. Inhibition of Golgi mannosidases (GMs) results in the transport of immature N-glycans to the cell surface. This can be employed to disrupt CCC. Here, we describe the molecular design and synthesis of an improved GM inhibitor with a non-sugar mimic scaffold that was screened from a compound library. The synthesized compounds were tested for enzyme inhibition ability and inhibition of spheroid formation using cell-based methods. Most of the compounds designed and synthesized exhibited GM inhibition at the cellular level. Of those, AR524 had higher inhibitory activity than a known GM inhibitor, kifunensine. Moreover, AR524 inhibited spheroid formation of human malignant cells at low concentration (10 µM), based on the disruption of CCC by GM inhibition. 相似文献
52.
《Current biology : CB》2020,30(8):1397-1409.e7
53.
54.
55.
《Bioorganic & medicinal chemistry》2020,28(2):115231
Sirtuins (SIRT1–SIRT7) are an evolutionary conserved family of NAD+-dependent protein deacylases regulating the acylation state of ε-N-lysine residues of proteins thereby controlling key biological processes. Numerous studies have found association of the aberrant enzymatic activity of SIRTs with various diseases like diabetes, cancer and neurodegenerative disorders. Previously, we have shown that substituted 2-alkyl-chroman-4-one/chromone derivatives can serve as selective inhibitors of SIRT2 possessing an antiproliferative effect in two human cancer cell lines. In this study, we have explored the bioisosteric replacement of the chroman-4-one/chromone core structure with different less lipophilic bicyclic scaffolds to overcome problems associated to poor physiochemical properties due to a highly lipophilic substitution pattern required for achieve a good inhibitory effect. Various new derivatives based on the quinolin-4(1H)-one scaffold, bicyclic secondary sulfonamides or saccharins were synthesized and evaluated for their SIRT inhibitory effect. Among the evaluated scaffolds, the benzothiadiazine-1,1-dioxide-based compounds showed the highest SIRT2 inhibitory activity. Molecular modeling studies gave insight into the binding mode of the new scaffold-replacement analogues. 相似文献
56.
An overview on the use of bile acid‐based compounds able to catalyze transformations, control the stereochemical course of a given reaction, recognize and bind other molecules, is presented. The recent developments in inclusion discrimination of chiral and achiral guests and enantioselective recognition achieved by bile acid are described with suitable examples. Chirality 2010. © 2009 Wiley‐Liss, Inc. 相似文献
57.
58.
59.
60.
Claire Molitor Beatrice Inthavong Lucile Sage Roberto A. Geremia & Bello Mouhamadou 《FEMS microbiology letters》2010,302(1):76-84
We explored the potential of the cox1 gene in the species resolution of soil fungi and compared it with the nuclear internal transcribed spacer (ITS) and small subunit (SSU)-rDNA. Conserved primers allowing the amplification of the fungal cox1 gene were designed, and a total of 47 isolates of Zygomycota and Ascomycota were investigated. The analysis revealed a lack of introns in >90% of the isolates. Comparison of the species of each of the six studied genera showed high interspecific sequence polymorphisms. Indeed, the average of nucleotide variations (4.2–11%) according to the genus, due mainly to the nucleotide substitutions, led to the taxonomic resolution of all the species studied regarding both ITS and SSU-rDNA, in which <88% were discriminated. The phylogenetic analysis performed after alignment of the cox1 gene across distant fungal species was in accordance with the well-known taxonomic position of the species studied and no overlap was observed between intra- and interspecific variations. These results clearly demonstrated that the cox1 sequences could provide good molecular markers for the determination of the species composition of environmental samples and constitute an important advance to study soil fungal biodiversity. 相似文献