全文获取类型
收费全文 | 113篇 |
免费 | 4篇 |
出版年
2019年 | 1篇 |
2018年 | 3篇 |
2017年 | 1篇 |
2016年 | 3篇 |
2015年 | 5篇 |
2014年 | 3篇 |
2013年 | 12篇 |
2012年 | 4篇 |
2011年 | 13篇 |
2010年 | 5篇 |
2009年 | 3篇 |
2008年 | 2篇 |
2007年 | 6篇 |
2006年 | 5篇 |
2005年 | 5篇 |
2004年 | 6篇 |
2003年 | 6篇 |
2002年 | 5篇 |
2000年 | 2篇 |
1999年 | 1篇 |
1998年 | 2篇 |
1997年 | 2篇 |
1996年 | 4篇 |
1994年 | 1篇 |
1993年 | 3篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1982年 | 2篇 |
1980年 | 1篇 |
1979年 | 3篇 |
1977年 | 2篇 |
排序方式: 共有117条查询结果,搜索用时 15 毫秒
61.
62.
Kim JS Krasieva TB LaMorte V Taylor AM Yokomori K 《The Journal of biological chemistry》2002,277(47):45149-45153
Cohesin is a conserved multiprotein complex that plays an essential role in sister chromatid cohesion. During interphase, cohesin is required for the establishment of cohesion following DNA replication. Because cohesin mutants resulted in increased sensitivity to DNA damage, a role for cohesin in DNA repair was also suggested. However, it was unclear whether this was due to general perturbation of cohesion or whether cohesin has a specialized role at the damage site. We therefore used a laser microbeam to create DNA damage at discrete sites in the cell nucleus and observed specific in vivo assembly of proteins at these sites by immunofluorescent detection. We observed that human cohesin is recruited to the damage site immediately after damage induction. Analysis of mutant cells revealed that cohesin recruitment to the damage site is dependent on the DNA double-strand break repair factor Mre11/Rad50 but not ATM or Nbs1. Consistently, Mre11/Rad50 and cohesin interact with each other in an interphase-specific manner. This interaction peaks in S/G(2) phase, during which cohesin is recruited to the DNA damage. Our results demonstrate the S/G(2)-specific and Mre11/Rad50-dependent recruitment of human cohesin to DNA damage, suggesting a specialized subfunction for cohesin in cell cycle-specific DNA double strand break repair. 相似文献
63.
White DG Hershey HP Moss JJ Daniels H Tuan RS Bennett VD 《Differentiation; research in biological diversity》2003,71(4-5):251-261
64.
65.
66.
Florentine Riquet Cathy Liautard‐Haag Lucy Woodall Carmen Bouza Patrick Louisy Bojan Hamer Francisco Otero‐Ferrer Philippe Aublanc Vickie Bduneau Olivier Briard Tahani El Ayari Sandra Hochscheid Khalid Belkhir Sophie Arnaud‐Haond Pierre‐Alexandre Gagnaire Nicolas Bierne 《Evolution; international journal of organic evolution》2019,73(4):817-835
Diverging semi‐isolated lineages either meet in narrow clinal hybrid zones, or have a mosaic distribution associated with environmental variation. Intrinsic reproductive isolation is often emphasized in the former and local adaptation in the latter, although both reduce gene flow between groups. Rarely are these two patterns of spatial distribution reported in the same study system. Here, we report that the long‐snouted seahorse Hippocampus guttulatus is subdivided into discrete panmictic entities by both types of hybrid zones. Along the European Atlantic coasts, a northern and a southern lineage meet in the southwest of France where they coexist in sympatry—i.e., in the same geographical zone—with little hybridization. In the Mediterranean Sea, two lineages have a mosaic distribution, associated with lagoon‐like and marine habitats. A fifth lineage was identified in the Black Sea. Genetic homogeneity over large spatial scales contrasts with isolation maintained in sympatry or close parapatry at a fine scale. A high variation in locus‐specific introgression rates provides additional evidence that partial reproductive isolation must be maintaining the divergence. We find that fixed differences between lagoon and marine populations in the Mediterranean Sea belong to the most differentiated SNPs between the two Atlantic lineages, against the genome‐wide pattern of structure that mostly follow geography. These parallel outlier SNPs cluster on a single chromosome‐wide island of differentiation. Since Atlantic lineages do not map to lagoon‐sea habitat variation, genetic parallelism at the genomic island suggests a shared genetic barrier contributes to reproductive isolation in contrasting contexts–i.e., spatial versus ecological. We discuss how a genomic hotspot of parallel differentiation could have evolved and become associated both with space and with a patchy environment in a single study system. 相似文献
67.
Increased aggression and activity level in 3- to 11-year-old girls with congenital adrenal hyperplasia (CAH) 总被引:2,自引:0,他引:2
Experimental research in a wide range of mammals has documented powerful influences of androgen during early development on brain systems and behaviors that show sex differences. Clinical research in humans suggests similar influences of early androgen concentrations on some behaviors, including childhood play behavior and adult sexual orientation. However, findings have been inconsistent for some other behaviors that show sex differences, including aggression and activity level in children. This inconsistency may reflect small sample sizes and assessment limitations. In the present study, we assessed aggression and activity level in 3- to 11-year-old children with CAH (38 girls, 29 boys) and in their unaffected siblings (25 girls, 21 boys) using a questionnaire that mothers completed to indicate current aggressive behavior and activity level in their children. Data supported the hypotheses that: (1) unaffected boys are more aggressive and active than unaffected girls; (2) girls with CAH are more aggressive and active than their unaffected sisters; and (3) boys with and without CAH are similar to one another in aggression and activity level. These data suggest that early androgens have a masculinizing effect on both aggressive behavior and activity level in girls. 相似文献
68.
Hong Seok Choi Vaibhav Jain Brian Krueger Vickie Marshall Chang Hee Kim Joanna L. Shisler Denise Whitby Rolf Renne 《PLoS pathogens》2015,11(11)
KSHV is a DNA tumor virus that causes Kaposi’s sarcoma. Upon KSHV infection, only a limited number of latent genes are expressed. We know that KSHV infection regulates host gene expression, and hypothesized that latent genes also modulate the expression of host miRNAs. Aberrant miRNA expression contributes to the development of many types of cancer. Array-based miRNA profiling revealed that all six miRNAs of the oncogenic miR-17-92 cluster are up-regulated in KSHV infected endothelial cells. Among candidate KSHV latent genes, we found that vFLIP and vCyclin were shown to activate the miR-17-92 promoter, using luciferase assay and western blot analysis. The miR-17-92 cluster was previously shown to target TGF-β signaling. We demonstrate that vFLIP and vCyclin induce the expression of the miR-17-92 cluster to strongly inhibit the TGF-β signaling pathway by down-regulating SMAD2. Moreover, TGF-β activity and SMAD2 expression were fully restored when antagomirs (inhibitors) of miR-17-92 cluster were transfected into cells expressing either vFLIP or vCyclin. In addition, we utilized viral genetics to produce vFLIP or vCyclin knock-out viruses, and studied the effects in infected TIVE cells. Infection with wildtype KSHV abolished expression of SMAD2 protein in these endothelial cells. While single-knockout mutants still showed a marked reduction in SMAD2 expression, TIVE cells infected by a double-knockout mutant virus were fully restored for SMAD2 expression, compared to non-infected TIVE cells. Expression of either vFLIP or vCycIin was sufficient to downregulate SMAD2. In summary, our data demonstrate that vFLIP and vCyclin induce the oncogenic miR-17-92 cluster in endothelial cells and thereby interfere with the TGF-β signaling pathway. Manipulation of the TGF-β pathway via host miRNAs represents a novel mechanism that may be important for KSHV tumorigenesis and angiogenesis, a hallmark of KS. 相似文献
69.
Terry D. Crawford Steffan Vartanian Alexandre Côté Steve Bellon Martin Duplessis E. Megan Flynn Michael Hewitt Hon-Ren Huang James R. Kiefer Jeremy Murray Christopher G. Nasveschuk Eneida Pardo F. Anthony Romero Peter Sandy Yong Tang Alexander M. Taylor Vickie Tsui Jian Wang David Stokoe 《Bioorganic & medicinal chemistry letters》2017,27(15):3534-3541
Bromodomain-containing protein 9 (BRD9), an epigenetic “reader” of acetylated lysines on post-translationally modified histone proteins, is upregulated in multiple cancer cell lines. To assess the functional role of BRD9 in cancer cell lines, we identified a small-molecule inhibitor of the BRD9 bromodomain. Starting from a pyrrolopyridone lead, we used structure-based drug design to identify a potent and highly selective in vitro tool compound 11, (GNE-375). While this compound showed minimal effects in cell viability or gene expression assays, it showed remarkable potency in preventing the emergence of a drug tolerant population in EGFR mutant PC9 cells treated with EGFR inhibitors. Such tolerance has been linked to an altered epigenetic state, and 11 decreased BRD9 binding to chromatin, and this was associated with decreased expression of ALDH1A1, a gene previously shown to be important in drug tolerance. BRD9 inhibitors may therefore show utility in preventing epigenetically-defined drug resistance. 相似文献
70.
Kuo BA Uporova TM Liang H Bennett VD Tuan RS Norton PA 《Journal of cellular biochemistry》2002,86(1):45-55
The alternative exon EIIIA of the fibronectin gene is included in mRNAs produced in undifferentiated mesenchymal cells but excluded from differentiated chondrocytes. As members of the SR protein family of splicing factors have been demonstrated to be involved in the alternative splicing of other mRNAs, the role of SR proteins in chondrogenesis-associated EIIIA splicing was investigated. SR proteins interacted with chick exon EIIIA sequences that are required for exon inclusion in a gel mobility shift assay. Addition of SR proteins to in vitro splicing reactions increased the rate and extent of exon EIIIA inclusion. Co-transfection studies employing cDNAs encoding individual SR proteins revealed that SRp20 decreased mRNA accumulation in HeLa cells, which make A+ mRNA, apparently by interfering with pre-mRNA splicing. Co-transfection studies also demonstrated that SRp40 increased exon EIIIA inclusion in chondrocytes, but not in HeLa cells, suggesting the importance of cellular context for SR protein activity. Immunoblot analysis did not reveal a relative depletion of SRp40 in chondrocytic cells. Possible mechanisms for regulation of EIIIA splicing in particular, and chondrogenesis associated splicing in general, are discussed. 相似文献