全文获取类型
收费全文 | 818篇 |
免费 | 28篇 |
国内免费 | 23篇 |
出版年
2023年 | 4篇 |
2022年 | 7篇 |
2021年 | 4篇 |
2020年 | 14篇 |
2019年 | 26篇 |
2018年 | 31篇 |
2017年 | 19篇 |
2016年 | 23篇 |
2015年 | 11篇 |
2014年 | 33篇 |
2013年 | 114篇 |
2012年 | 7篇 |
2011年 | 24篇 |
2010年 | 18篇 |
2009年 | 26篇 |
2008年 | 29篇 |
2007年 | 35篇 |
2006年 | 32篇 |
2005年 | 33篇 |
2004年 | 30篇 |
2003年 | 31篇 |
2002年 | 23篇 |
2001年 | 24篇 |
2000年 | 16篇 |
1999年 | 21篇 |
1998年 | 25篇 |
1997年 | 27篇 |
1996年 | 18篇 |
1995年 | 16篇 |
1994年 | 14篇 |
1993年 | 11篇 |
1992年 | 6篇 |
1991年 | 9篇 |
1990年 | 12篇 |
1989年 | 12篇 |
1988年 | 8篇 |
1987年 | 6篇 |
1986年 | 4篇 |
1985年 | 12篇 |
1984年 | 12篇 |
1983年 | 4篇 |
1982年 | 13篇 |
1981年 | 10篇 |
1980年 | 5篇 |
1979年 | 2篇 |
1977年 | 3篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 2篇 |
1973年 | 1篇 |
排序方式: 共有869条查询结果,搜索用时 281 毫秒
41.
Daniel Ladurée Christine Fossey Zoica Delbederi Elena Sugeac Sylvie Schmidt Geraldine Laumond 《Journal of enzyme inhibition and medicinal chemistry》2013,28(6):533-549
We have previously reported the synthesis and evaluation of potent anti-human immunodeficiency virus compounds based on β-D-d4T analogues bearing a tether attached at the C-5 position and their β-L-counterparts. Initial study revealed a requirement for an alkyl side-chain with an optimal length of 12 carbons for a weak antiviral activity. As a continuation of that work, we have now prepared the corresponding phosphoramidate derivatives as possible membrane-permeable prodrugs. Phosphorochloridate chemistry gave the target phosphoramidates which were tested for anti-human immunodeficiency virus type 1 activity; unfortunately, they were devoid of anti-HIV activity. 相似文献
42.
《Nucleosides, nucleotides & nucleic acids》2013,32(5-8):911-914
Abstract Tricyclic (T) analogues of acyclovir (ACV, 1) and ganciclovir (GCV, 2) carrying the 3,9-dihydro-9-oxo-5H-imidazo[1,2-a]purine system [i.e., 6-(4-BrPh)TACV, 5 and 6-(4-BrPh)TGCV, 6] were transformed into 6-[(4′-R2)-4-biphenylyl] derivatives of TACV (7–9) and TGCV (10–12) by Suzuki cross coupling with 4-substituted phenylboronic acids. Compound 11 (R2 = CH2OH) showed a high (~1000) selectivity index against herpes simplex virus type 1 (HSV-1) together with advantageous fluorescence properties (emission in visible region, little overlap with absorption and moderate intensity). 相似文献
43.
《Nucleosides, nucleotides & nucleic acids》2013,32(8-9):1499-1502
In the present study, we investigated the effect of fluoropyrimidines on the growth of Ureaplasma urealyticum. Addition of fluoropyrimidines strongly inhibited bacterial growth. Growth inhibition by these analogues could be reversed by addition of either thymidine or deoxyuridine, suggesting inhibition of thymidylate biosynthesis as the mechanism in operation. 相似文献
44.
V. Vivet-Boudou J.-C. Paillart A. Burger R. Marquet 《Nucleosides, nucleotides & nucleic acids》2013,32(6-7):743-746
With the emergence of HIV strains resistant or cross-resistant to nearly all antiretroviral regimen, novel therapy approaches have to be considered. As a part of our current work on viral mutagenic compounds, we prepared 1-(2′ -deoxy-β-D-ribofuranosyl)-1,2,4-triazole-3-carboxamide (2′ -deoxy-ribavirin) and its 5′ -triphosphate derivative. The nucleoside mutagenic activity was evaluated on HIV-1 NL4-3 in CEMx174 cell culture. After 2.5 months, no reduction on HIV-1 viability was observed. On the other hand, in vitro experiments with purified HIV-1 RT demonstrated that the triphosphate analog can be incorporated opposite to several natural nucleosides. 相似文献
45.
46.
《Nucleosides, nucleotides & nucleic acids》2013,32(5-8):623-627
Abstract Preparation of the nucleoside analogues 1 and incorporation of 1, B = T, in deoxyribooligonucleotides by the phosphoramidite method is described. A two-step deprotection procedure was developed to reduce cleavage of the modified allylic unit. The binding properties of the modified oligonucleotides towards complementary DNA and RNA has been evaluated by Tm measurements showing a ΔTm of ?2 to ?6.5°C per modification. An oligonucleotide with two modifications at the 3′-end showed considerable resistance towards cleavage by a 3′-exonuclease. No antiviral activity against HIV-1 or HSV-1 was found for 1, B = G or T, or for any of the trihydroxy derivatives 5. 相似文献
47.
Jennifer Sigmond Godefridus J. Peters 《Nucleosides, nucleotides & nucleic acids》2013,32(10-12):1997-2022
In anti-cancer treatment, deoxynucleoside analogues are widely used in combination chemotherapy. Improvement can be achieved by rational design of novel combinations with cell cycle inhibitors. These compounds inhibit protein kinases, preventing the cell cycle from continuing when affected by deoxynucleoside analogs. The efficacy is dependent on the site of cell cycle inhibition, whether multiple cyclin-dependent kinases are inhibited and whether the inhibitors should be given before or after the deoxynucleoside analogs. The action of cell cycle inhibition in vivo may be limited by unfavorable pharmacokinetics. Preclinical and clinical studies will be discussed, aiming to design improved future strategies. 相似文献
48.
Vladimir A. Efimov Oksana G. Chakhmakhcheva Eric Wickstrom 《Nucleosides, nucleotides & nucleic acids》2013,32(10-12):1853-1874
Negatively charged DNA mimics containing phosphonate analogues of peptide nucleic acids were designed, and their physicochemical and biological properties were evaluated in the comparison with natural oligonucleotides, classical peptide nucleic acids, and morpholino phosphorodiamidate oligonucleotide analogues. The results obtained revealed a high potential of phosphonate-containing PNA derivatives for a number of biological applications, such as diagnostic, nucleic acids analysis, and inhibition of gene expression. 相似文献
49.
Panagiotis Ioannidis Björn Classon Bertil Samuelsson Ingemar Kvarnström 《Nucleosides, nucleotides & nucleic acids》2013,32(5):449-462
Abstract 1-(2,3-Dideoxy-2-C-hydroxymethyl-β-D-threo-pentofuranosyl)-, 1-(2,3-didehydro-2,3-dideoxy-2-C-hydroxymethyl-β-D-glycero-pentofuranosyl)- and 1-(2-C-azidomethyl-2,3-didehydro-2,3-dideoxy-β-D-glycero-pentofuranosyl)uracuracil, thymine and cytosine were synthesized and evaluated for their anti-HIV activities. A key step of the synthesis involves a novel alcohol transposition of2-methylene-nucleoside analogues. 相似文献
50.
A. D. Adema L. Zuurbier K. Floor I. Hubeek G. J. L. Kaspers F. Albertoni 《Nucleosides, nucleotides & nucleic acids》2013,32(9-11):981-986
Troxacitabine is a cytotoxic deoxycytidine analogue with an unnatural L-configuration, which is activated by deoxycytidine kinase (dCK). The configuration is responsible for differences in the uptake and metabolism of troxacitabine compared to other deoxynucleoside analogues. To determine whether troxacitabine has an advantage over other nucleoside analogues several cell lines resistant to cladribine and gemcitabine were exposed to troxacitabine, while blast cells from pediatric leukemia patients were tested for cross-resistance with other deoxynucleoside analogues. The gemcitabine resistant AG6000 (IC50: >3000 nM), and the cladribine resistant CEM (IC50: 150 nM) and HL-60 (IC50: >3000 nM) cell lines, all with no or decreased dCK expression, were less sensitive to troxacitabine than their wild type counterparts (IC50; A2780: 410, CEM: 71 and HL-60: 158 nM). dCK protein expression in CEM was higher than in HL-60, which, in turn, was higher than in A2780. Catalytically inactive p53 seems to increase the sensitivity to troxacitabine. The patient samples showed a large range of sensitivity to troxacitabine, similar to other deoxynucleoside analogues. Cross-resistance with all other deoxynucleoside analogues was observed. 相似文献