全文获取类型
收费全文 | 192篇 |
免费 | 10篇 |
出版年
2023年 | 1篇 |
2022年 | 1篇 |
2021年 | 4篇 |
2020年 | 3篇 |
2019年 | 2篇 |
2018年 | 5篇 |
2017年 | 5篇 |
2016年 | 3篇 |
2015年 | 9篇 |
2014年 | 12篇 |
2013年 | 18篇 |
2012年 | 13篇 |
2011年 | 4篇 |
2010年 | 11篇 |
2009年 | 6篇 |
2008年 | 10篇 |
2007年 | 9篇 |
2006年 | 7篇 |
2005年 | 9篇 |
2004年 | 10篇 |
2003年 | 4篇 |
2002年 | 6篇 |
2001年 | 4篇 |
2000年 | 4篇 |
1999年 | 6篇 |
1998年 | 2篇 |
1997年 | 2篇 |
1993年 | 2篇 |
1992年 | 1篇 |
1991年 | 3篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1988年 | 4篇 |
1987年 | 3篇 |
1986年 | 6篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 3篇 |
1979年 | 2篇 |
1970年 | 1篇 |
排序方式: 共有202条查询结果,搜索用时 15 毫秒
121.
122.
Jeffrey D. Cooney Gordon J. Hildick-Smith Ebrahim Shafizadeh Paul F. McBride Kelli J. Carroll Heidi Anderson George C. Shaw Owen J. Tamplin Diana S. Branco Arthur J. Dalton Dhvanit I. Shah Clara Wong Patrick G. Gallagher Leonard I. Zon Trista E. North Barry H. Paw 《Developmental biology》2013,373(2):431-441
123.
Krzysztof Domagalski Ma?gorzata Paw?owska Dorota Kozielewicz Dorota Dybowska Andrzej Tretyn Waldemar Halota 《PloS one》2015,10(6)
The strong impact of interleukin 28B (IL28B) polymorphisms on sustained virological response (SVR) after peginterferon and ribavirin treatment in patients with chronic hepatitis C (CHC) is well-known. We investigated IL28B variability and hepatic expression of IP10, IFI27, ISG15, and MX1 in CHC patients, the relation of each with their clinical characteristics, and how they associated with responses to combined therapy. Genotyping and gene expression analysis were conducted in a selected cohort of treatment-naïve patients who underwent interferon and ribavirin treatment. Differential expression of IP10, IFI27, ISG15, and MX1 genes was assessed from pretreatment liver biopsies using quantitative PCR. Histopathological evaluation of liver specimens was performed on the basis of the Scheuer’s modified scale. We showed that hepatic IFI27, ISG15, and MX1 expression was lower in the IL28B CC 12979860 and TT rs8099917 groups than in the CT-TT rs12979860 and TG-GG rs8099917 groups (P < 0.001). We found no differences in IP10 expression between the IL28B genotypes (P > 0.05); in contrast, IP10 expression was significantly affected by the progression of fibrosis (P = 0.007). We showed that the rs12979860 CC genotype was associated with successful treatment when compared to the rs12979860 CT-TT genotype (P = 0.004). Additionally, the expression levels of IP10, IFI27 and ISG15, but not MX1, were significantly higher in non-SVR patients than in SVR patients. The effect of variation in IL28B on the results of IFN-based treatment may be associated with changes in IFI27 and ISG15, but not with IP10. Silencing of IP10 is positive and independent from IL28B prediction of SVR, which is strongly associated with liver fibrosis in CHC patients. 相似文献
124.
125.
Sobkowiak-Tabaka Iwona Pawłowski Dominik Milecka Krystyna Kubiak-Martens Lucy Kostecki Robert Janczak-Kostecka Beata Goslar Tomasz Ratajczak-Szczerba Magdalena 《Vegetation History and Archaeobotany》2020,29(2):153-171
Vegetation History and Archaeobotany - The results of high-resolution records of pollen, plant macroremains and charred plant particles, diatoms, Cladocera and geochemistry from a 14C-dated core,... 相似文献
126.
Magdalena Król Karol M Paw?owski Katarzyna Szyszko Henryk Maciejewski Izabella Dolka Elisabetta Manuali Micha? Jank Tomasz Motyl 《BMC veterinary research》2012,8(1):1-22
Background
It is supposed that fibroblasts present in tumour microenvironment increase cancer invasiveness and its ability to metastasize but the mechanisms have not been clearly defined yet. Thus, the current study was designed to assess changes in gene expression in five various cancer cell lines grown as a co-culture with the carcinoma-associated fibroblasts (CAFs) in vitro.Results
A carcinoma-associated fibroblast cell line was isolated from a canine mammary cancer. Then, a co-culture of cancer cells with the CAFs was established and maintained for 72 hrs. Having sorted the cells, a global gene expression in cancer cells using DNA microarrays was examined. The analysis revealed an up-regulation of 100 genes and a down-regulation of 106 genes in the cancer cells grown as a co-culture with the CAFs in comparison to control conditions. The PANTHER binomial statistics tool was applied to determine statistically over-manifested pathways (p < 0.05). Bulk of the up-regulated genes are involved in the adhesion, the angiogenesis, the epithelial-mesenchymal transition (EMT) and generally take part in the developmental processes. These results were further confirmed using real-time qPCR. Moreover, a wound-healing assay and growth characteristics on Matrigel matrix showed that CAFs increase cancer cell migration and matrix invasion.Conclusion
The results of the current study showed that the co-culturing of cancer cells and the CAFs caused significant changes to the cancer gene expression. The presence of the CAFs in a microenvironment of cancer cells promotes adhesion, angiogenesis and EMT. 相似文献127.
Selenoproteins serve important functions in many organisms, usually providing essential oxidoreductase enzymatic activity, often for defense against toxic xenobiotic substances. Most eukaryotic genomes possess a small number of these proteins, usually not more than 20. Selenoproteins belong to various structural classes, often related to oxidoreductase function, yet a few of them are completely uncharacterised.Here, the structural and functional prediction for the uncharacterised selenoprotein O (SELO) is presented. Using bioinformatics tools, we predict that SELO protein adopts a three-dimensional fold similar to protein kinases. Furthermore, we argue that despite the lack of conservation of the "classic" catalytic aspartate residue of the archetypical His-Arg-Asp motif, SELO kinases might have retained catalytic phosphotransferase activity, albeit with an atypical active site. Lastly, the role of the selenocysteine residue is considered and the possibility of an oxidoreductase-regulated kinase function for SELO is discussed.The novel kinase prediction is discussed in the context of functional data on SELO orthologues in model organisms, FMP40 a.k.a.YPL222W (yeast), and ydiU (bacteria). Expression data from bacteria and yeast suggest a role in oxidative stress response. Analysis of genomic neighbourhoods of SELO homologues in the three domains of life points toward a role in regulation of ABC transport, in oxidative stress response, or in basic metabolism regulation. Among bacteria possessing SELO homologues, there is a significant over-representation of aquatic organisms, also of aerobic ones. The selenocysteine residue in SELO proteins occurs only in few members of this protein family, including proteins from Metazoa, and few small eukaryotes (Ostreococcus, stramenopiles). It is also demonstrated that enterobacterial mchC proteins involved in maturation of bactericidal antibiotics, microcins, form a distant subfamily of the SELO proteins.The new protein structural domain, with a putative kinase function assigned, expands the known kinome and deserves experimental determination of its biological role within the cell-signaling network. 相似文献
128.
Tomasz A Paw?owski 《BMC plant biology》2009,9(1):48
Background
Seed dormancy is controlled by the physiological or structural properties of a seed and the external conditions. It is induced as part of the genetic program of seed development and maturation. Seeds with deep physiological embryo dormancy can be stimulated to germinate by a variety of treatments including cold stratification. Hormonal imbalance between germination inhibitors (e.g. abscisic acid) and growth promoters (e.g. gibberellins) is the main cause of seed dormancy breaking. Differences in the status of hormones would affect expression of genes required for germination. Proteomics offers the opportunity to examine simultaneous changes and to classify temporal patterns of protein accumulation occurring during seed dormancy breaking and germination. Analysis of the functions of the identified proteins and the related metabolic pathways, in conjunction with the plant hormones implicated in seed dormancy breaking, would expand our knowledge about this process. 相似文献129.
Discovery of Genes Essential for Heme Biosynthesis through Large-Scale Gene Expression Analysis 总被引:1,自引:0,他引:1
130.
David C. Hess Chad L. Myers Curtis Huttenhower Matthew A. Hibbs Alicia P. Hayes Jadine Paw John J. Clore Rosa M. Mendoza Bryan San Luis Corey Nislow Guri Giaever Michael Costanzo Olga G. Troyanskaya Amy A. Caudy 《PLoS genetics》2009,5(3)
Mitochondria are central to many cellular processes including respiration, ion homeostasis, and apoptosis. Using computational predictions combined with traditional quantitative experiments, we have identified 100 proteins whose deficiency alters mitochondrial biogenesis and inheritance in Saccharomyces cerevisiae. In addition, we used computational predictions to perform targeted double-mutant analysis detecting another nine genes with synthetic defects in mitochondrial biogenesis. This represents an increase of about 25% over previously known participants. Nearly half of these newly characterized proteins are conserved in mammals, including several orthologs known to be involved in human disease. Mutations in many of these genes demonstrate statistically significant mitochondrial transmission phenotypes more subtle than could be detected by traditional genetic screens or high-throughput techniques, and 47 have not been previously localized to mitochondria. We further characterized a subset of these genes using growth profiling and dual immunofluorescence, which identified genes specifically required for aerobic respiration and an uncharacterized cytoplasmic protein required for normal mitochondrial motility. Our results demonstrate that by leveraging computational analysis to direct quantitative experimental assays, we have characterized mutants with subtle mitochondrial defects whose phenotypes were undetected by high-throughput methods. 相似文献