全文获取类型
收费全文 | 415篇 |
免费 | 10篇 |
国内免费 | 1篇 |
出版年
2022年 | 1篇 |
2021年 | 6篇 |
2020年 | 8篇 |
2019年 | 7篇 |
2018年 | 12篇 |
2017年 | 15篇 |
2016年 | 13篇 |
2015年 | 11篇 |
2014年 | 6篇 |
2013年 | 10篇 |
2012年 | 32篇 |
2011年 | 32篇 |
2010年 | 20篇 |
2009年 | 19篇 |
2008年 | 25篇 |
2007年 | 22篇 |
2006年 | 26篇 |
2005年 | 22篇 |
2004年 | 14篇 |
2003年 | 9篇 |
2002年 | 15篇 |
2001年 | 14篇 |
2000年 | 5篇 |
1999年 | 5篇 |
1998年 | 3篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1995年 | 3篇 |
1992年 | 7篇 |
1991年 | 3篇 |
1990年 | 5篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1982年 | 1篇 |
1978年 | 2篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1973年 | 4篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1968年 | 1篇 |
1967年 | 4篇 |
1966年 | 1篇 |
1965年 | 1篇 |
1954年 | 2篇 |
1952年 | 10篇 |
1951年 | 11篇 |
1950年 | 8篇 |
排序方式: 共有426条查询结果,搜索用时 156 毫秒
71.
I B Krasnov 《Tsitologiia》1973,15(12):1535-1539
72.
V. M. Blinov G. S. Krasnov A. V. Shargunov M. A. Shurdov V. V. Zverev 《Molecular Biology》2013,47(5):613-621
Immunosuppressive domains (ISDs) of viral envelope glycoproteins provide highly pathogenic phenotypes to various retroviruses. The ISD interaction with immune cells leads to an inhibition of the response. As was shown in the 1980s, a 17-amino acid residue of ISD fragment (known as CKS-17) is responsible for this immune modulation. However, the underlying mechanisms were unknown. Thorough research identified activation of signal transduction via the Ras-Raf-MEK-MAPK and PI3K-AKT-mTOR cell pathways as a result of the ISD interaction with immune cells. The result is the decrease in the secretion of stimulatory cytokines (e.g., IL-12) and increase of inhibitory and anti-inflammatory cytokines (e.g., IL-10). One of the receptor tyrosine kinases that triggers signal transduction in these pathways acts as a primary ISD target, while other key regulators, cAMP and diacylglycerol (DAG), act as secondary messengers. Immunosuppressive-like domains are not restricted to retroviruses; an ISD present in Ebola virus envelope glycoproteins determines an extremely severe clinical course of virus-induced hemorrhagic fever. A number of retrovirus-originating ISD-coding regions are found in the human genome. The regions are expressed as parts of the syncytin genes in the placenta, helping to render the mother’s immune system tolerant of the placenta and embryo. The review considers the molecular aspects of the retroviral ISD-induced modulation of the host immune system. 相似文献
73.
74.
A. V. Snezhkina G. S. Krasnov S. O. Zhikrivetskaya I. Y. Karpova M. S. Fedorova K. M. Nyushko M. M. Belyakov N. V. Gnuchev D. V. Sidorov B. Y. Alekseev N. V. Melnikova A. V. Kudryavtseva 《Molecular Biology》2018,52(2):190-199
Glycolysis activation is one of the main features of energy metabolism in cancer cells that is associated with the increase in glycolytic enzyme synthesis, primarily, hexokinases (HKs), in many types of tumors. Conversely, in colorectal cancer (CRC) the decrease in the expression of HK2 gene, which encodes one of the key rate-limiting enzyme of glycolysis, was revealed, thus, the study of the mechanisms of its inhibition in CRC is of particular interest. To search for potential microRNAs, inhibiting the expression of HK2 in CRC, we have performed the analysis of data from “The Cancer Genome Atlas” (TCGA) and five microRNA–mRNA target interaction databases (TargetScan, DIANA microT, mirSVR (miRanda), PicTar, and miRTarBase) using original CrossHub software. Seven microRNAs containing binding site on mRNA HK2, which expression is negatively correlated with HK2 expression, were selected for further analysis. The expression levels of these microRNAs and mRNA HK2 were estimated by quantitative PCR on a set of CRC samples. It has been shown, that the expression of three microRNAs (miR-9-5p, -98-5p, and -199-5p) was increased and correlated negatively with mRNA level of HK2 gene. Thus, downregulation of HK2 gene may be caused by its negative regulation through microRNAs miR-9-5p, -98-5p, and -199-5p. 相似文献
75.
The genetic variability at six cloned minisatellite loci was analyzed in
minke whale populations from the North Atlantic, North Pacific, and
Antarctic Oceans. Three loci displayed only a few different alleles in each
of the three populations, with heterozygosity ranging from 0.00 to 0.47,
and three loci revealed many different alleles in at least two fo the three
populations, with heterozygosity ranging up to 0.98. Using small sample
sizes, samples from two adjacent Antarctic Management Areas were not found
to differ significantly in allele frequencies at any of the six loci. The
use of principal coordinate analysis to detect multilocus disequilibria was
explored. No significant evidence was found of intrapopulation
heterogeneity within the pooled Antarctic sample. Pronounced interoceanic
differences were observed at every locus, confirming the existence of
genetic isolation found earlier using more conventional marker systems. The
populations from the three oceans appear to have diverged to such a degree
that the hypervariable loci have had time to evolve independently and
arrive at different evolutionary stages in different populations. The
frequency of undetected "null" alleles is remarkably high in minke whale
populations compared to human populations and is probably a result of the
cloning protocol used. Minisatellite loci are shown to provide a powerful
population genetic tool, supplying levels of resolution appropriate to
different degrees of evolutionary divergence.
相似文献
76.
N. I. Smirnova T. A. Kul’shan’ E. Yu. Baranikhina Ya. M. Krasnov D. A. Agafonov V. V. Kutyrev 《Russian Journal of Genetics》2016,52(9):914-925
Intraspecies genetic differentiation of nontoxigenic strains of Vibrio cholerae of El Tor biovar containing one of the key pathogenicity genes, tcpA, is studied along with the phylogenetic relationships between these strains and toxigenic isolates. Comparative analysis of the whole genome nucleotide sequences demonstrates for the first time that ctxA–tcpA+ strains vary considerably and can be clustered into two separate groups, the CTXφ–RS1φ+VPI+VSP+/CTXφ–RS1φ–VPI+VSP+ isolates and the CTXφ–RS1φ–VPI+VSP– isolates, differing in their epidemiological significance. In the course of model experiments, it is established that nontoxigenic potentially epidemic CTXφ–RS1φ+VPI+VSP+/CTXφ–RS1φ–VPI+VSP+ isolates are derivatives of toxigenic strains. The results of whole genome SNP analysis of 35 Vibrio cholerae strains confirm these data and indicate genetic remoteness of nontoxigenic CTXφ–RS1φ–VPI+VSP– strains both from the potentially epidemic strains and from the toxigenic isolates. It is found that the genomes of the CTXφ–RS1φ–VPI+VSP– strains contain unique SNPs which are characteristic of them alone. The new data on the structure of the genome of nontoxigenic strains with different epidemiological significance may be further used for their genetic differentiation. 相似文献
77.
Yaroslav G. Gurskiy David G. Garbuz Nataliya V. Soshnikova Aleksey N. Krasnov Alexei Deikin Vladimir F. Lazarev Dmitry Sverchinskyi Boris A. Margulis Olga G. Zatsepina Vadim L. Karpov Svetlana N. Belzhelarskaya Evgenia Feoktistova Sofia G. Georgieva Michael B. Evgen’ev 《Cell stress & chaperones》2016,21(6):1055-1064
The production of major human heat shock protein Hsp70 (HSPA1A) in a eukaryotic expression system is needed for testing and possible medical applications. In this study, transgenic mice were produced containing wild-type human Hsp70 allele in the vector providing expression in the milk. The results indicated that human Hsp70 was readily expressed in the transgenic animals but did not apparently preserve its intact structure and, hence, it was not possible to purify the protein using conventional isolation techniques. It was suggested that the protein underwent glycosylation in the process of expression, and this quite common modification for proteins expressed in the milk complicated its isolation. To check this possibility, we mutated all presumptive sites of glycosylation and tested the properties of the resulting modified Hsp70 expressed in E. coli. The investigation demonstrated that the modified protein exhibited all beneficial properties of the wild-type Hsp70 and was even superior to the latter for a few parameters. Based on these results, a transgenic mouse strain was obtained which expressed the modified Hsp70 in milk and which was easy to isolate using ATP columns. Therefore, the developed construct can be explored in various bioreactors for reliable manufacture of high quality, uniform, and reproducible human Hsp70 for possible medical applications including neurodegenerative diseases and cancer. 相似文献
78.
Trait‐based and phylogenetic associations between parasites and their hosts: a case study with small mammals and fleas in the Palearctic 下载免费PDF全文
We investigated the associations between ecological (density, shelter structure), morphological (body mass, hair morphology) and physiological traits (basal metabolic rate) of small mammals and ecological (seasonality of reproduction, microhabitat preferences, abundance, host specificity) and morphological (presence and number of combs) traits of their flea parasites that shape host selection processes by fleas. We adapted the extended version of the three‐table ordination and linked species composition of flea assemblages of host species with traits and phylogenies of both hosts and fleas. Fleas with similar trait values, independent of phylogenetic affinities, were clustered on the same host species. Fleas possessing certain traits selected hosts possessing certain traits. Fleas belonging to the same phylogenetic lineage were found on the same host more often than expected by chance. Certain phylogenetic lineages of hosts harbored certain phylogenetic lineages of fleas. The process of host selection by fleas appeared to be determined by reciprocal relationships between host and flea traits, as well as between host and flea phylogenies. We concluded that the connection between host and flea phylogenies, coupled with the connection between host and flea traits, suggests that the species compositions of the host spectra of fleas were driven by the interaction between historical processes and traits. 相似文献
79.
A. D. Beniaminov G. S. Krasnov A. A. Dmitriev G. A. Puzanov B. A. Snopok V. N. Senchenko V. I. Kashuba 《Molecular Biology》2016,50(3):438-441
Earlier we established that CTDSPL gene encoding small carboxy-terminal domain serine phosphatase can be considered a classical tumor suppressor gene. Besides, transfection of tumor cell line MCF-7 with CTDSPL led to the content decrease of inactive phosphorylated form of another tumor suppressor, retinoblastoma protein (Rb), and subsequently to cell cycle arrest at the G1/S boundary. This result implied that small phosphatase CTDSPL is able to specifically dephosphorylate and activate Rb protein. In order to add some fuel to this hypothesis, in the present work we studied the interaction of two tumor suppressors CTDSPL and Rb in vitro. GST pool-down assay revealed that CTDSPL is able to precipitate Rb protein from MCF-7 cell extracts, while surface plasmon resonance technique showed that interaction of the two proteins is direct. Results of this study reassert that phosphatase CTDSPL and Rb could be involved in the common mechanism of cell cycle regulation. 相似文献
80.