全文获取类型
收费全文 | 123篇 |
免费 | 5篇 |
出版年
2021年 | 2篇 |
2020年 | 1篇 |
2019年 | 1篇 |
2018年 | 2篇 |
2017年 | 1篇 |
2016年 | 4篇 |
2015年 | 8篇 |
2014年 | 5篇 |
2013年 | 7篇 |
2012年 | 17篇 |
2011年 | 12篇 |
2010年 | 4篇 |
2008年 | 7篇 |
2007年 | 4篇 |
2006年 | 4篇 |
2005年 | 4篇 |
2004年 | 1篇 |
2003年 | 2篇 |
2002年 | 2篇 |
2001年 | 1篇 |
1999年 | 1篇 |
1995年 | 1篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 9篇 |
1989年 | 12篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1977年 | 1篇 |
1973年 | 2篇 |
排序方式: 共有128条查询结果,搜索用时 15 毫秒
1.
Sundari Chetty Elise N. Engquist Elie Mehanna Kathy O. Lui Alexander M. Tsankov Douglas A. Melton 《The Journal of cell biology》2015,210(7):1257-1268
Driving human pluripotent stem cells (hPSCs) into specific lineages is an inefficient and challenging process. We show that a potent Src inhibitor, PP1, regulates expression of genes involved in the G1 to S phase transition of the cell cycle, activates proteins in the retinoblastoma family, and subsequently increases the differentiation propensities of hPSCs into all three germ layers. We further demonstrate that genetic suppression of Src regulates the activity of the retinoblastoma protein and enhances the differentiation potential of hPSCs across all germ layers. These positive effects extend beyond the initial germ layer specification and enable efficient differentiation at subsequent stages of differentiation. 相似文献
2.
3.
4.
Etienne Karita Matt A Price Shabir Lakhi William Kilembe Anatoli Kamali Eugene Ruzagira Eric Hunter Paul Farmer Susan Allen Gwynn Stevens Paramesh Chetty Sabrina Welsh Annie Yang Jill Gilmour Pat Fast The IAVI Africa HIV Prevention Partnership 《PloS one》2015,10(8)
Background
2013 WHO guidelines recommend starting ART at CD4+ T-cell counts ≤500 cells/μL. We present the T-cell counts from adult Africans with HIV shortly following transmission to their sexual partners.Methods
HIV-discordant couples in Zambia, Uganda and Rwanda were followed prospectively and received couples counseling and condoms. HIV uninfected partners were tested for HIV at least quarterly and HIV-infected partners received HIV care and referral for ART per national guidelines. Upon diagnosis of incident HIV infection in the previously HIV-uninfected partner, a blood sample was collected from both partners to measure CD4+ T-cells and perform viral linkage. The estimated date of infection (EDI) of the incident case was calculated based on testing history. EDI was unknown for suspected transmitting partners.Results
From 2006–2011, 4,705 HIV-discordant couples were enrolled in this cohort, and 443 cases of incident HIV infection were documented. Virus linkage analysis was performed in 374 transmission pairs, and 273 (73%) transmissions were linked genetically. CD4 counts in the transmitting partner were measured a median of 56 days after EDI (mean:90.5, min:10, max:396). The median CD4 count was 339 cells/μl (mean:386.4, min:15, max:1,434), and the proportion of partners with a CD4+ T-cell count above 500/μl was 25% (95% CI:21, 31).Conclusions
In our cohort of discordant couples, 73% of HIV transmissions occurred within the relationship, and the transmitter CD4+ T cell count shortly after the transmission event was frequently higher than the WHO 2013 ART-initiation guidelines. 相似文献5.
Carryn Chetty Thandokuhle Khumalo Bianca Da Costa Dias Uwe Reusch Stefan Knackmuss Melvyn Little Stefan F. T. Weiss 《PloS one》2014,9(5)
Two key events, namely adhesion and invasion, are pivotal to the occurrence of metastasis. Importantly, the 37 kDa/67 kDa laminin receptor (LRP/LR) has been implicated in enhancing these two events thus facilitating cancer progression. In the current study, the role of LRP/LR in the adhesion and invasion of liver cancer (HUH-7) and leukaemia (K562) cells was investigated. Flow cytometry revealed that the HUH-7 cells displayed significantly higher cell surface LRP/LR levels compared to the poorly-invasive breast cancer (MCF-7) control cells, whilst the K562 cells displayed significantly lower cell surface LRP/LR levels in comparison to the MCF-7 control cells. However, Western blotting and densitometric analysis revealed that all three tumorigenic cell lines did not differ significantly with regards to total LRP/LR levels. Furthermore, treatment of liver cancer cells with anti-LRP/LR specific antibody IgG1-iS18 (0.2 mg/ml) significantly reduced the adhesive potential of cells to laminin-1 and the invasive potential of cells through the ECM-like Matrigel, whilst leukaemia cells showed no significant differences in both instances. Additionally, Pearson''s correlation coefficients suggested direct proportionality between cell surface LRP/LR levels and the adhesive and invasive potential of liver cancer and leukaemia cells. These findings suggest the potential use of anti-LRP/LR specific antibody IgG1-iS18 as an alternative therapeutic tool for metastatic liver cancer through impediment of the LRP/LR- laminin-1 interaction. 相似文献
6.
Ram R Chetty M 《IEEE/ACM transactions on computational biology and bioinformatics / IEEE, ACM》2011,8(2):353-367
An efficient two-step Markov blanket method for modeling and inferring complex regulatory networks from large-scale microarray data sets is presented. The inferred gene regulatory network (GRN) is based on the time series gene expression data capturing the underlying gene interactions. For constructing a highly accurate GRN, the proposed method performs: 1) discovery of a gene's Markov Blanket (MB), 2) formulation of a flexible measure to determine the network's quality, 3) efficient searching with the aid of a guided genetic algorithm, and 4) pruning to obtain a minimal set of correct interactions. Investigations are carried out using both synthetic as well as yeast cell cycle gene expression data sets. The realistic synthetic data sets validate the robustness of the method by varying topology, sample size, time delay, noise, vertex in-degree, and the presence of hidden nodes. It is shown that the proposed approach has excellent inferential capabilities and high accuracy even in the presence of noise. The gene network inferred from yeast cell cycle data is investigated for its biological relevance using well-known interactions, sequence analysis, motif patterns, and GO data. Further, novel interactions are predicted for the unknown genes of the network and their influence on other genes is also discussed. 相似文献
7.
8.
Krishna Kumar Veeravalli Chandramu Chetty Shivani Ponnala Christopher S. Gondi Sajani S. Lakka Daniel Fassett Jeffrey D. Klopfenstein Dzung H. Dinh Meena Gujrati Jasti S. Rao 《PloS one》2010,5(7)
Background
Involvement of MMP-9, uPAR and cathepsin B in adhesion, migration, invasion, proliferation, metastasis and tumor growth has been well established. In the present study, MMP-9, uPAR and cathepsin B genes were downregulated in glioma xenograft cells using shRNA plasmid constructs and we evaluated the involvement of integrins and changes in their adhesion, migration and invasive potential.Methodology/Principal Findings
MMP-9, uPAR and cathepsin B single shRNA plasmid constructs were used to downregulate these molecules in xenograft cells. We also used MMP-9/uPAR and MMP-9/cathepsin B bicistronic constructs to evaluate the cumulative effects. MMP-9, uPAR and cathepsin B downregulation significantly inhibits xenograft cell adhesion to several extracellular matrix proteins. Treatment with MMP-9, uPAR and cathepsin B shRNA of xenografts led to the downregulation of several alpha and beta integrins. In all the assays, we noticed more prominent effects with the bicistronic plasmid constructs when compared to the single plasmid shRNA constructs. FACS analysis demonstrated the expression of αVβ3, α6β1 and α9β1 integrins in xenograft cells. Treatment with bicistronic constructs reduced αVβ3, α6β1 and α9β1 integrin expressions in xenograft injected nude mice. Migration and invasion were also inhibited by MMP-9, uPAR and cathepsin B shRNA treatments as assessed by spheroid migration, wound healing, and Matrigel invasion assays. As expected, bicistronic constructs further inhibited the adhesion, migration and invasive potential of the xenograft cells as compared to individual treatments.Conclusions/Significance
Downregulation of MMP-9, uPAR and cathespin B alone and in combination inhibits adhesion, migration and invasive potential of glioma xenografts by downregulating integrins and associated signaling molecules. Considering the existence of integrin inhibitor-resistant cancer cells, our study provides a novel and effective approach to inhibiting integrins by downregulating MMP-9, uPAR and cathepsin B in the treatment of glioma. 相似文献9.
Smith JA Kohn TA Chetty AK Ojuka EO 《American journal of physiology. Endocrinology and metabolism》2008,295(3):E698-E704
The role of CaMK II in regulating GLUT4 expression in response to intermittent exercise was investigated. Wistar rats completed 5 x 17-min bouts of swimming after receiving 5 mg/kg KN93 (a CaMK II inhibitor), KN92 (an analog of KN93 that does not inhibit CaMK II), or an equivalent volume of vehicle. Triceps muscles that were harvested at 0, 6, or 18 h postexercise were assayed for 1) CaMK II phosphorylation by Western blot, 2) acetylation of histone H3 at the Glut4 MEF2 site by chromatin immunoprecipitation (ChIP) assay, 3) bound MEF2A at the Glut4 MEF2 cis-element by ChIP, and 4) GLUT4 expression by RT-PCR and Western blot. Compared with controls, exercise caused a twofold increase in CaMK II phosphorylation. Immunohistochemical stains indicated increased CaMK II phosphorylation in nuclear and perinuclear regions of the muscle fiber. Acetylation of histone H3 in the region surrounding the MEF2 binding site on the Glut4 gene and the amount of MEF2A that bind to the site increased approximately twofold postexercise. GLUT4 mRNA and protein increased approximately 2.2- and 1.8-fold, respectively, after exercise. The exercise-induced increases in CaMK II phosphorylation, histone H3 acetylation, MEF2A binding, and GLUT4 expression were attenuated or abolished when KN93 was administered to rats prior to exercise. KN92 did not affect the increases in pCaMK II and GLUT4. These data support the hypothesis that CaMK II activation by exercise increases GLUT4 expression via increased accessibility of MEF2A to its cis-element on the gene. 相似文献
10.
Extensive intrasubtype recombination in South African human immunodeficiency virus type 1 subtype C infections 下载免费PDF全文
Rousseau CM Learn GH Bhattacharya T Nickle DC Heckerman D Chetty S Brander C Goulder PJ Walker BD Kiepiela P Korber BT Mullins JI 《Journal of virology》2007,81(9):4492-4500
Recombinant human immunodeficiency virus type 1 (HIV-1) strains containing sequences from different viral genetic subtypes (intersubtype) and different lineages from within the same subtype (intrasubtype) have been observed. A consequence of recombination can be the distortion of the phylogenetic signal. Several intersubtype recombinants have been identified; however, less is known about the frequency of intrasubtype recombination. For this study, near-full-length HIV-1 subtype C genomes from 270 individuals were evaluated for the presence of intrasubtype recombination. A sliding window schema (window, 2 kb; step, 385 bp) was used to partition the aligned sequences. The Shimodaira-Hasegawa test detected significant topological incongruence in 99.6% of the comparisons of the maximum-likelihood trees generated from each sequence partition, a result that could be explained by recombination. Using RECOMBINE, we detected significant levels of recombination using five random subsets of the sequences. With a set of 23 topologically consistent sequences used as references, bootscanning followed by the interactive informative site test defined recombination breakpoints. Using two multiple-comparison correction methods, 47% of the sequences showed significant evidence of recombination in both analyses. Estimated evolutionary rates were revised from 0.51%/year (95% confidence interval [CI], 0.39 to 0.53%) with all sequences to 0.46%/year (95% CI, 0.38 to 0.48%) with the putative recombinants removed. The timing of the subtype C epidemic origin was revised from 1961 (95% CI, 1947 to 1962) with all sequences to 1958 (95% CI, 1949 to 1960) with the putative recombinants removed. Thus, intrasubtype recombinants are common within the subtype C epidemic and these impact analyses of HIV-1 evolution. 相似文献