全文获取类型
收费全文 | 1142篇 |
免费 | 57篇 |
国内免费 | 1篇 |
出版年
2024年 | 1篇 |
2023年 | 4篇 |
2022年 | 10篇 |
2021年 | 18篇 |
2020年 | 8篇 |
2019年 | 18篇 |
2018年 | 23篇 |
2017年 | 11篇 |
2016年 | 22篇 |
2015年 | 53篇 |
2014年 | 69篇 |
2013年 | 68篇 |
2012年 | 128篇 |
2011年 | 91篇 |
2010年 | 67篇 |
2009年 | 56篇 |
2008年 | 77篇 |
2007年 | 80篇 |
2006年 | 93篇 |
2005年 | 67篇 |
2004年 | 59篇 |
2003年 | 52篇 |
2002年 | 37篇 |
2001年 | 11篇 |
2000年 | 6篇 |
1999年 | 5篇 |
1998年 | 6篇 |
1997年 | 9篇 |
1996年 | 6篇 |
1995年 | 3篇 |
1994年 | 2篇 |
1993年 | 4篇 |
1992年 | 6篇 |
1991年 | 1篇 |
1990年 | 4篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 3篇 |
1981年 | 1篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1973年 | 3篇 |
1972年 | 1篇 |
1933年 | 4篇 |
排序方式: 共有1200条查询结果,搜索用时 31 毫秒
991.
The ketoenamine-enolimine tautometic equilibrium has been studied by the analysis of aromaticity and electron-topological
parameters. The influence of substituents on the energy of the transition state and of the tautomeric forms has been investigated
for different positions of chelate chain. The quantum theory of atoms in molecules method (QTAIM) has been applied to study
changes in the electron-topological parameters of the molecule with respect to the tautomeric equilibrium in intramolecular
hydrogen bond. Dependencies of the HOMA aromaticity index and electron density at the critical points defining aromaticity
and electronic state of the chelate chain on the transition state (TS), OH and HN tautomeric forms have been obtained. 相似文献
992.
993.
We hypothesized that DNA damage products (5'R)-8,5'-cyclo-2'-deoxyadenosine (R-cdA) and (5'S)-8,5'-cyclo-2'-deoxyadenosine (S-cdA) may be well-suited biomarkers of risk and diagnosis for atherosclerosis. We tested this hypothesis by measuring the levels of R-cdA and S-cdA and another product, 8-hydroxy-2'-deoxyguanosine (8-OH-dG), in urine of atherosclerosis patients and healthy individuals using liquid chromatography-tandem mass spectrometry with isotope dilution. We showed the presence of these products at significantly greater concentrations in urine of atherosclerosis patients than in that of healthy individuals. Our data suggest that R-cdA and S-cdA can be accurately and reproducibly measured in human urine as potential biomarkers of risk and diagnosis for atherosclerosis. 相似文献
994.
Pawel Stocki Maxime Sawicki Charles E. Mays Seo Jung Hong Daniel C. Chapman David Westaway David B. Williams 《Molecular biology of the cell》2016,27(5):757-767
Prion diseases are fatal neurodegenerative disorders for which there is no effective treatment. Because the cellular prion protein (PrPC) is required for propagation of the infectious scrapie form of the protein, one therapeutic strategy is to reduce PrPC expression. Recently FK506, an inhibitor of the FKBP family of peptidyl prolyl isomerases, was shown to increase survival in animal models of prion disease, with proposed mechanisms including calcineurin inhibition, induction of autophagy, and reduced PrPC expression. We show that FK506 treatment results in a profound reduction in PrPC expression due to a defect in the translocation of PrPC into the endoplasmic reticulum with subsequent degradation by the proteasome. These phenotypes could be bypassed by replacing the PrPC signal sequence with that of prolactin or osteopontin. In mouse cells, depletion of ER luminal FKBP10 was almost as potent as FK506 in attenuating expression of PrPC. However, this occurred at a later stage, after translocation of PrPC into the ER. Both FK506 treatment and FKBP10 depletion were effective in reducing PrPSc propagation in cell models. These findings show the involvement of FKBP proteins at different stages of PrPC biogenesis and identify FKBP10 as a potential therapeutic target for the treatment of prion diseases. 相似文献
995.
Alicja Kuban-Jankowska Kamlesh K. Sahu Magdalena Gorska Pawel Niedzialkowski Jack A. Tuszynski Tadeusz Ossowski Michal Wozniak 《World journal of microbiology & biotechnology》2016,32(10):163
Yersinia sp. bacteria owe their viability and pathogenic virulence to the YopH factor, which is a highly active bacterial protein tyrosine phosphatase. Inhibition of YopH phosphatase results in the lack of Yersinia sp. pathogenicity. We have previously described that aurintricarboxylic acid inhibits the activity of YopH at nanomolar concentrations and represents a unique mechanism of YopH inactivation due to a redox process. This work is a continuation of our previous studies. Here we show that modifications of the structure of aurintricarboxylic acid reduce the ability to inactivate YopH and lead to higher cytotoxicity. In the present paper we examine the inhibitory properties of aurintricarboxylic acid analogues, such as eriochrome cyanine R (ECR) and pararosaniline. Computational docking studies we report here indicate that ATA analogues are not precluded to bind in the YopH active site and in all obtained binding conformations ECR and pararosaniline bind to YopH active site. The free binding energy calculations show that ECR has a stronger binding affinity to YopH than pararosaniline, which was confirmed by experimental YopH enzymatic activity studies. We found that ATA analogues can reversibly reduce the enzymatic activity of YopH, but possess weaker inhibitory properties than ATA. The ATA analogues induced inactivation of YopH is probably due to oxidative mechanism, as pretreatment with catalase prevents from inhibition. We also found that ATA analogues significantly decrease the viability of macrophage cells, especially pararosaniline, while ATA reveals only slight effect on cell viability. 相似文献
996.
Garay E Jankowski P Lizano P Marczak S Maehr H Adorini L Uskokovic MR Studzinski GP 《Bioorganic & medicinal chemistry》2007,15(13):4444-4455
997.
998.
999.
Miazek A Cebula A Skwarek M Cebrat M Kisielow P 《Biochemical and biophysical research communications》2007,358(2):483-488
Molecular cloning of targeting vectors (TgVs) is a prerequisite procedure for gene disruption in embryonic stem cells. In cases where target genes display complex features (e.g., gene overlap, alternative exon usage), TgVs must mediate deletions with very high precision to prevent unwanted effects. This is often difficult to achieve by procedures using restriction endonucleases and DNA ligases. Therefore, to prepare TgVs for inactivation of two complex genes of immunological interest: PTPRF and NWC, we employed an alternative method, which involves engineering bacterial artificial chromosomes (BACs) by inducible, plasmid encoded "Red/ET recombinase" expression system. Here, we report rapid and efficient construction of PTPRF and NWC TgVs without using restriction endonucleases. 相似文献
1000.