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排序方式: 共有134条查询结果,搜索用时 15 毫秒
21.
An P Wang LH Hutcheson-Dilks H Nelson G Donfield S Goedert JJ Rinaldo CR Buchbinder S Kirk GD O'Brien SJ Winkler CA 《PLoS pathogens》2007,3(6):e88
Human cyclophilin A, or CypA, encoded by the gene peptidyl prolyl isomerase A (PPIA), is incorporated into the HIV type 1 (HIV-1) virion and promotes HIV-1 infectivity by facilitating virus uncoating. We examined the effect of single nucleotide polymorphisms (SNPs) and haplotypes within the PPIA gene on HIV-1 infection and disease progression in five HIV-1 longitudinal history cohorts. Kaplan-Meier survival statistics and Cox proportional hazards model were used to assess time to AIDS outcomes. Among eight SNPs tested, two promoter SNPs (SNP3 and SNP4) in perfect linkage disequilibrium were associated with more rapid CD4(+) T-cell loss (relative hazard = 3.7, p = 0.003) in African Americans. Among European Americans, these alleles were also associated with a significant trend to more rapid progression to AIDS in a multi-point categorical analysis (p = 0.005). Both SNPs showed differential nuclear protein-binding efficiencies in a gel shift assay. In addition, one SNP (SNP5) located in the 5' UTR previously shown to be associated with higher ex vivo HIV-1 replication was found to be more frequent in HIV-1-positive individuals than in those highly exposed uninfected individuals. These results implicate regulatory PPIA polymorphisms as a component of genetic susceptibility to HIV-1 infection or disease progression, affirming the important role of PPIA in HIV-1 pathogenesis. 相似文献
22.
An P Duggal P Wang LH O'Brien SJ Donfield S Goedert JJ Phair J Buchbinder S Kirk GD Winkler CA 《PLoS genetics》2007,3(1):e19
Human apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (Apobec3) antiretroviral factors cause hypermutation of proviral DNA leading to degradation or replication-incompetent HIV-1. However, HIV-1 viral infectivity factor (Vif) suppresses Apobec3 activity through the Cullin 5-Elongin B-Elongin C E3 ubiquitin ligase complex. We examined the effect of genetic polymorphisms in the CUL5 gene (encoding Cullin 5 protein) on AIDS disease progression in five HIV-1 longitudinal cohorts. A total of 12 single nucleotide polymorphisms (SNPs) spanning 93 kb in the CUL5 locus were genotyped and their haplotypes inferred. A phylogenetic network analysis revealed that CUL5 haplotypes were grouped into two clusters of evolutionarily related haplotypes. Cox survival analysis and mixed effects models were used to assess time to AIDS outcomes and CD4(+) T cell trajectories, respectively. Relative to cluster I haplotypes, the collective cluster II haplotypes were associated with more rapid CD4(+) T cell loss (relative hazards [RH] = 1.47 and p = 0.009), in a dose-dependent fashion. This effect was mainly attributable to a single cluster II haplotype (Hap10) (RH = 2.49 and p = 0.00001), possibly due to differential nuclear protein-binding efficiencies of a Hap10-specifying SNP as indicated by a gel shift assay. Consistent effects were observed for CD4(+) T cell counts and HIV-1 viral load trajectories over time. The findings of both functional and genetic epidemiologic consequences of CUL5 polymorphism on CD4(+) T cell and HIV-1 levels point to a role for Cullin 5 in HIV-1 pathogenesis and suggest interference with the Vif-Cullin 5 pathway as a possible anti-HIV-1 therapeutic strategy. 相似文献
23.
Wagner R Leschonsky B Harrer E Paulus C Weber C Walker BD Buchbinder S Wolf H Kalden JR Harrer T 《Journal of immunology (Baltimore, Md. : 1950)》1999,162(6):3727-3734
It has been hypothesized that sequence variation within CTL epitopes leading to immune escape plays a role in the progression of HIV-1 infection. Only very limited data exist that address the influence of biologic characteristics of CTL epitopes on the emergence of immune escape variants and the efficiency of suppression HIV-1 by CTL. In this report, we studied the effects of HIV-1 CTL epitope sequence variation on HIV-1 replication. The highly conserved HLA-B14-restricted CTL epitope DRFYKTLRAE in HIV-1 p24 was examined, which had been defined as the immunodominant CTL epitope in a long-term nonprogressing individual. We generated a set of viral mutants on an HX10 background differing by a single conservative or nonconservative amino acid substitution at each of the P1 to P9 amino acid residues of the epitope. All of the nonconservative amino acid substitutions abolished viral infectivity and only 5 of 10 conservative changes yielded replication-competent virus. Recognition of these epitope sequence variants by CTL was tested using synthetic peptides. All mutations that abrogated CTL recognition strongly impaired viral replication, and all replication-competent viral variants were recognized by CTL, although some variants with a lower efficiency. Our data indicate that this CTL epitope is located within a viral sequence essential for viral replication. Targeting CTL epitopes within functionally important regions of the HIV-1 genome could limit the chance of immune evasion. 相似文献
24.
Delgado JC Leung JY Baena A Clavijo OP Vittinghoff E Buchbinder S Wolinsky S Addo M Walker BD Yunis EJ Goldfeld AE 《Immunogenetics》2003,55(7):497-501
Control of HIV-1 viremia and progression to AIDS has been associated with specific HLA genes. The tumor necrosis factor (TNF) and the non-classical major histocompatibility (MHC) class I chain-related A (MICA) genes are located in the genomic segment between the HLA class I and II genes and variants of both genes have been identified. We thus analyzed TNF promoter and MICA variants in a well-characterized group of HIV-1 infected individuals with different abilities to control HIV-1 viremia. In our cohort, the –1030/–862-linked TNF promoter single-nucleotide polymorphisms (SNPs), but not MICA variants, are significantly associated with lack of control of HIV-1 viremia (P=0.03). This association is independent of those HLA-B35 alleles associated with HIV-1 disease progression with which the –862 TNF SNP has previously been independently associated. Thus, non-randomly associated genes near the TNF locus are likely involved in control of HIV-1 viremia. 相似文献
25.
Type IX collagen is a key component of the extracellular matrix of
cartilage where it occurs at the surfaces of type II collagen fibrils as a
glycanated molecule. The function of the glycosaminoglycan (GAG) side chain
of the molecule is, however, unknown. We have shown that type IX collagen
in chicken sternal cartilage is synthesized with a unimodal distribution of
GAG chain size, but at post 17 days of development three predominant
glycanforms of type IX collagen accumulate. Such accumulation did not occur
in sterna from day 15 embryos. In day 17 embryos predominant glycanforms
were found in the caudal region of the sternum. By day 19 of development
the three predominant glycanforms are widespread throughout the caudal and
cephalic regions. The results indicate that developmental and anatomical
changes occur to type IX collagen that depend on the size of the GAG chain
attached to the alpha2(IX) chain of the molecule.
相似文献
26.
Synergistic neutralization of human immunodeficiency virus type 1 by combinations of human monoclonal antibodies. 总被引:12,自引:10,他引:2 下载免费PDF全文
S Laal S Burda M K Gorny S Karwowska A Buchbinder S Zolla-Pazner 《Journal of virology》1994,68(6):4001-4008
The ability of antibodies to the V3 region and the CD4-binding domain (CD4bd) of human immunodeficiency virus type 1 (HIV-1) to act in synergy to neutralize HIV has been demonstrated previously. However, synergy between antibodies to other HIV-1 epitopes has not been studied. We have used 21 combinations of human monoclonal antibodies (MAbs) directed against different epitopes of the gp120 and gp41 proteins of HIV-1 to evaluate their ability to act in synergy to neutralize HIV-1. Combinations of anti-V3 and anti-CD4bd antibodies, anti-V3 and anti-gp120 C-terminus antibodies, anti-CD4bd and anti-C-terminus antibodies, anti-V3 and anti-gp41 antibodies, and anti-CD4bd and anti-gp41 antibodies were tested. Our results show that some, but not all anti-V3 antibodies can act in synergy with anti-CD4bd antibodies. In addition, for the first time, antibodies to the C-terminus region have been found to act in synergy with the anti-CD4bd antibodies. Various anti-CD4bd MAbs also act in synergy when used together. The use of such cocktails of human MAbs for passive immunization against HIV-1 may prove to be important for therapy in postexposure settings and for prevention of maternal-fetal transmission of the virus. The results also provide information on the types of antibodies that should be elicited by an effective vaccine. 相似文献
27.
Coordinate regulation of the four tubulin genes of Chlamydomonas reinhardi. 总被引:18,自引:2,他引:16 下载免费PDF全文
During cell division and during the induction of tubulin synthesis that accompanies flagellar regeneration in Chlamydomonas reinhardi, four tubulin mRNAs of discrete molecular sizes are produced. During induction two beta tubulin mRNAs (2.47 kb and 2.34 kb) and two alpha tubulin mRNAs (2.26 kb and 2.13 kb) are synthesized in high abundance and in a closely coordinated fashion. Combined data from restriction enzyme mapping (i.e., Southern analysis) of genomic DNA and of Charon 30 recombinant clones bearing inserts of Chlamydomonas tubulin genes provide direct evidence for four distinct tubulin genes in this organism. Dot-blot analysis of the level of hybridization of a 32p nick-translated beta tubulin cDNA to genomic DNA from gametic cells and to a clone containing the beta 1 tubulin gene indicate that each beta 1 tubulin gene is present in one copy per cell. Additional hybridization experiments employing fragments of cDNA clones which selectively anneal to either the 3' or 5' portions of the two alpha tubulin genes or to one or both of the two beta tubulin genes suggest that each tubulin gene is actively transcribed to give rise to one of the four tubulin mRNAs. These observations further suggest that at most four basic types of tubulin subunits are produced by Chlamydomonas and that the heterogeneity of tubulin subunits reported to exist in the flagellar axoneme must arise as a result of post-translational modification. 相似文献
28.
Association of DC-SIGN promoter polymorphism with increased risk for parenteral, but not mucosal, acquisition of human immunodeficiency virus type 1 infection 总被引:5,自引:0,他引:5 下载免费PDF全文
Martin MP Lederman MM Hutcheson HB Goedert JJ Nelson GW van Kooyk Y Detels R Buchbinder S Hoots K Vlahov D O'Brien SJ Carrington M 《Journal of virology》2004,78(24):14053-14056
There is considerable debate about the fundamental mechanisms that underlie and restrict acquisition of human immunodeficiency virus type 1 (HIV-1) infection. In light of recent studies demonstrating the ability of C type lectins to facilitate infection with HIV-1, we explored the potential relationship between polymorphisms in the DC-SIGN promoter and risk for acquisition of HIV-1 according to route of infection. Using samples obtained from 1,611 European-American participants at risk for parenteral (n = 713) or mucosal (n = 898) infection, we identified single-nucleotide polymorphisms in the DC-SIGN promoter using single-strand conformation polymorphism. Individuals at risk for parenterally acquired infection who had -336C were more susceptible to infection than were persons with -336T (odds ratio = 1.87, P = 0.001). This association was not observed in those at risk for mucosally acquired infection. A potential role for DC-SIGN specific to systemic acquisition and dissemination of infection is suggested. 相似文献
29.
Altfeld MA Livingston B Reshamwala N Nguyen PT Addo MM Shea A Newman M Fikes J Sidney J Wentworth P Chesnut R Eldridge RL Rosenberg ES Robbins GK Brander C Sax PE Boswell S Flynn T Buchbinder S Goulder PJ Walker BD Sette A Kalams SA 《Journal of virology》2001,75(3):1301-1311
Virus-specific cytotoxic T-lymphocyte (CTL) responses are critical in the control of human immunodeficiency virus type 1 (HIV-1) infection and will play an important part in therapeutic and prophylactic HIV-1 vaccines. The identification of virus-specific epitopes that are efficiently recognized by CTL is the first step in the development of future vaccines. Here we describe the immunological characterization of a number of novel HIV-1-specific, HLA-A2-restricted CTL epitopes that share a high degree of conservation within HIV-1 and a strong binding to different alleles of the HLA-A2 superfamily. These novel epitopes include the first reported CTL epitope in the Vpr protein. Two of the novel epitopes were immunodominant among the HLA-A2-restricted CTL responses of individuals with acute and chronic HIV-1 infection. The novel CTL epitopes identified here should be included in future vaccines designed to induce HIV-1-specific CTL responses restricted by the HLA-A2 superfamily and will be important to assess in immunogenicity studies in infected persons and in uninfected recipients of candidate HIV-1 vaccines. 相似文献
30.
Yunda Huang Dean Follmann Martha Nason Lily Zhang Ying Huang Devan V. Mehrotra Zoe Moodie Barbara Metch Holly Janes Michael C. Keefer Gavin Churchyard Merlin L. Robb Patricia E. Fast Ann Duerr M. Juliana McElrath Lawrence Corey John R. Mascola Barney S. Graham Magdalena E. Sobieszczyk James G. Kublin Michael Robertson Scott M. Hammer Glenda E. Gray Susan P. Buchbinder Peter B. Gilbert 《PloS one》2015,10(9)