全文获取类型
收费全文 | 158篇 |
免费 | 10篇 |
专业分类
168篇 |
出版年
2021年 | 1篇 |
2019年 | 3篇 |
2018年 | 1篇 |
2017年 | 3篇 |
2016年 | 4篇 |
2015年 | 4篇 |
2014年 | 5篇 |
2013年 | 14篇 |
2012年 | 4篇 |
2011年 | 9篇 |
2010年 | 3篇 |
2009年 | 2篇 |
2008年 | 7篇 |
2007年 | 9篇 |
2006年 | 8篇 |
2005年 | 9篇 |
2004年 | 19篇 |
2003年 | 7篇 |
2002年 | 3篇 |
2001年 | 10篇 |
2000年 | 11篇 |
1999年 | 6篇 |
1998年 | 2篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1992年 | 2篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 3篇 |
1980年 | 2篇 |
1978年 | 2篇 |
1969年 | 1篇 |
排序方式: 共有168条查询结果,搜索用时 15 毫秒
31.
Patutina O Mironova N Ryabchikova E Popova N Nikolin V Kaledin V Vlassov V Zenkova M 《Biochimie》2011,93(4):689-696
Recent data on the involvement of miRNA and circulating tumor-derived DNA in regulation of tumorigenesis showed a great prospect for these molecules as a novel class of therapeutic targets and gave a new start for the study of enzymes cleaving nucleic acids as potential antitumor and antimetastatic agents. In the present paper using two murine tumor models with pulmonary or liver metastases we studied the antimetastatic potential of RNase A and DNase I and performed a search for possible molecular targets of the enzymes. Herein, we show for the first time that daily administration of ultralow doses of RNase A (0.5-50 μg/kg) and DNase I (0.02-2.3 mg/kg) inhibits the development of metastasis to 60-90% and RNase A exerts 30% retardation of tumor growth. Remarkably, the increase in RNase A dose from 50 μg/kg to 10 mg/kg leads to a disappearance of antitumor and antimetastatic effects. Simultaneous treatment of tumor-bearing animals with RNase A and DNase I leads to an additive effect and results in almost total absence of metastases. The use of RNase A as an adjuvant in conjunction with conventional cytostatic cyclophosphamide results in a reliable enhancement of antitumor and antimetastatic effect of the therapy compared with the use of these agents individually. The search for possible molecular mechanism of antimetastatic effect of nucleases showed that daily administration of the enzymes reduced the pathologically increased level of extracellular nucleic acids and increased nuclease activity of the blood plasma of tumor-bearing mice back to the level of healthy animals. Thus, we unequivocally show that the proposed protocol of treatment of tumor-bearing animals with RNase A and DNase I has a general systemic and immunomodulatory effect, leads to a drastic suppression of metastasis development, and in perspective may become an effective component of intensive complex therapy of cancer. 相似文献
32.
M. A. Zenkova N. L. Chumakova A. V. Vlassov N. I. Komarova A. G. Venyaminova V. V. Vlassov V. N. Silnikov 《Molecular Biology》2000,34(3):390-394
The mechanism of hydrolysis of RNA substrates—diribonucleoside monophosphate CpA and decaribonucleotide UUCAUGUAAA—by chemical
constructs functionally mimicking ribonuclease A was studied. It is shown that RNA cleavage by chemical RNases 2L2 and 2D3
proceeds similar to the RNase A-induced RNA hydrolysis through 2′,3′-cyclophosphate as an intermediate product. A comparison
of hydrolyses of CpA in water and D2O revealed an isotope effect (K
H/K
D=2.28), which implies acid-base catalysis at the limiting stage of the reaction. Two feasible mechanisms of RNA hydrolysis
by chemical RNases (linear and adjacent) are discussed. 相似文献
33.
E L Chernolovskaya N D Kobets R G Borissov T V Abramova V V Vlassov 《FEBS letters》1992,303(2-3):269-271
Reaction of 4-(N-2-chloroethyl-N-methylamino)benzylphosphamides of oligonucleotides (RCl-(pT)16 and RCl-(pApC)6) with human chromatin in intact nuclei and with metaphase chromosomes has been investigated. The oligonucleotides were targeted to poly(A) and poly(TG)-repeating DNA sequences. It was found that the reagents alkylate DNA and some proteins due to specific complex formation. The affinity character of the reaction was proved by the fact that free corresponding oligonucleotides taken in excess or preliminary treatment of chromatin with S1-nuclease both prevent the biopolymers from modification. The results obtained evidence that in human chromatin there are open DNA sequences available for affinity modification with oligonucleotide derivatives. Analysis of patterns of modified proteins within these chromatin areas may give a key to the structure of these chromatin sites. 相似文献
34.
Olga V. Gvozdeva Vladimir S. Prassolov Marina A. Zenkova Valentin V. Vlassov 《Nucleosides, nucleotides & nucleic acids》2016,35(8):389-403
Overexpression of inducible subunits of immunoproteasome is related to pathogenesis of some chronic diseases. Specific inhibition of the immunosubunits may be used for the treatment of these diseases and RNA interference is one of the potent methods used in this area. We designed 2′-O-methyl modified siRNAs with selectively protected nuclease-sensitive sites, which efficiently silence LMP2, LMP7, and MECL-1 genes expression. To provide stable long-lasting inhibition of target genes, short-hairpin RNAs (shRNA) expressed by lentiviral vectors were constructed. Our results demonstrated that chemically modified siRNAs inhibited the expression of target genes with similar efficiency or with efficiency exceeding that of corresponding shRNAs and provide silencing effect for 5 days. 相似文献
35.
Complementary addressed modification and cleavage of a single stranded DNA fragment with alkylating oligonucleotide derivatives. 总被引:4,自引:2,他引:2 下载免费PDF全文
V V Vlassov V F Zarytova I V Kutiavin S V Mamaev M A Podyminogin 《Nucleic acids research》1986,14(10):4065-4076
A single stranded DNA fragment was modified with alkylating derivatives of oligonucleotides complementary to a certain nucleotide sequences in the fragment. The derivatives carried aromatic 2-chloroethylamino groups at their 3'- or 5'-terminal nucleotide residues. Some of the derivatives carried both alkylating group and intercalating phenazine group which stabilized complementary complexes. It was found that these oligonucleotide derivatives modify the DNA fragment in a specific way near the target complementary nucleotide sequences, and the DNA fragment can be cleaved at the alkylated nucleotides positions. Alkylating derivatives carrying phenazine groups were found to be the most efficient in reaction with the DNA fragment. 相似文献
36.
A S Boutorin L V Gus'kova E M Ivanova N D Kobetz V F Zarytova A S Ryte L V Yurchenko V V Vlassov 《FEBS letters》1989,254(1-2):129-132
5'-[32P]-labelled alkylating decathymidylate [4-(N-2-chloroethyl)N-methylaminobenzyl]-5'-phosphamide derivatives containing cholesterol or phenazinium residues at their 3'-termini were synthesized and used for alkylation of DNA within mammalian cells. The uptake of the cholesterol derivative by the cells and the extent of DNA alkylation are about two orders of magnitude higher than those of a similar alkylating derivative lacking the groups at the 3'-termini. The presence of the phenazinium residue at the 3'-terminus of the oligonucleotide reagent does not improve the reagent uptake by the cells but drastically increases the DNA modification efficiency. 相似文献
37.
Laktionov PP Tamkovich SN Rykova EY Bryzgunova OE Starikov AV Kuznetsova NP Sumarokov SV Kolomiets SA Sevostianova NV Vlassov VV 《Nucleosides, nucleotides & nucleic acids》2004,23(6-7):879-883
The concentration of extracellular DNA and RNA in blood plasma of healthy donors, trauma patients, patients with breast and lung cancer, nonmalignant breast tumors and nonmalignant lung diseases were estimated. Significant amounts of extracellular RNA were found in plasma of trauma patients. The concentration of DNA and RNA in plasma of trauma patients correlates with the extent of posttraumatic organ failure. Extracellular RNA was not found in the plasma of breast cancer patients and patients with nonmalignant breast tumors, whereas a very high concentration of extracellular RNA was found in patients with malignant and nonmalignant diseases of lung. 相似文献
38.
Development of efficient methods for synthesis of oligonucleotides and oligonucleotide analogs has opened up the possibility of designing a broad spectrum of affinity reagents for specific modification of nucleic acids and proteins. These affinity reagents are used for investigation of the topology of ribosomes and nucleic acid polymerases. Oligonucleotides and their analogs are already used for suppression of specific gene expression and for elucidation of the physiological role of their products. Oligonucleotide derivatives appear to offer considerable promise as potential gene-targeted drugs such as antivirals and specific inhibitors of oncogene expression. 相似文献
39.
Mironova NL Pyshnyi DV Stadler DV Prokudin IV Boutorine YI Ivanova EM Zenkova MA Gross HJ Vlassov VV 《Journal of biomolecular structure & dynamics》2006,23(6):591-602
Artificial ribonucleases, conjugates of short oligodeoxyribonucleotides and peptides built of arginine, leucine, proline, and serine, were synthesized and assessed in terms of ribonuclease activity and specificity of RNA cleavage. A specific group of the conjugates was identified that display T1-ribonuclease-like activity and cleave RNA predominantly at G-X sequences. Circular dichroism study of the structures of the most active conjugates, free peptide (LR)4G, and oligonucleotides revealed that conjugation of oligonucleotide to the peptide results in a specific peptide folding that possibly provides ribonuclease activity to the conjugate. 相似文献
40.
Makel'Skaya MV Koval OA Kobets ND Vlassov VV 《Antisense & nucleic acid drug development》1999,9(6):533-536
Oligonucleotide derivatives capable of binding to specific nucleic acids are considered as potential therapeutic agents, exerting their action at the level of genome functioning (Hélène, 1991; Knorre et al., 1993). A straightforward approach to targeting DNA is based on using oligonucleotides capable of binding to oligopurine-oligopyrimidine sequences by formation of triple-strand structures. We report results of experiments on sequence-specific chemical modification of a 490-bp fragment of pfosCAT plasmid, containing the promoter segment of the c-fos gene using 4-(N-2-chloroethyl-N-methylamino)-benzylphosphamide derivatives of a homopyrimidine 14-mer oligonucleotide. It was shown that in both the free DNA and the DNA involved in nucleosome structure, reaction occurred with similar efficiency at the target guanosine residue G404. 相似文献