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41.
Manuel Medarde Ana B.S. Maya Concepción Pérez-Melero 《Journal of enzyme inhibition and medicinal chemistry》2013,28(6):521-540
Synthesis and evaluation of new combretastatin analogues with varied modifications on the bridge and the aromatic rings, have shown that the 2-naphthyl moiety is a good surrogate for the 3-hydroxy-4-methoxyphenyl (B-ring) of combretastatin A-4. Other bicyclic systems, such as 6(7)-quinolyl and 5-indolyl, can replace the B-ring, but they produce less potent analogues in the cytotoxicity and tubulin polymerization inhibition assays. Other modifications are detrimentral for the potency of the studied analogues. The 2-naphthyl combretastatin 53 and the related 6-quinolyl combretastatin 106 analogues are the most potent among the derivatives of this type, whereas 92 and 95 are the most potent among the naphthalene derivatives with a heterocycle in the bridge. Previous and new results in this family of combretastatin analogues are discussed. 相似文献
42.
Leixiang Yang Jingxu Gong Feng Wang Yongmin Zhang Yanguang Wang Xiaojiang Hao 《Journal of enzyme inhibition and medicinal chemistry》2013,28(4):399-404
In this work, we evaluated the antioxidant properties of the eight novel silybin analogues for their capacity to scavenge free radicals including superoxide anion radicals and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals in vitro. Compound 7d demonstrated an excellent antioxidant effect in scavenging superoxide anion free radical with an IC50 value of 26.5 μM, while the IC50 of quercetin (the reference compound) was 38.1 μM. Compounds 7b, 7e, 7h showed certain scavenging activities for both types of free radicals. 相似文献
43.
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
44.
《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
45.
《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
46.
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
47.
48.
《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
49.
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
50.
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