全文获取类型
收费全文 | 284篇 |
免费 | 17篇 |
国内免费 | 3篇 |
专业分类
儿科学 | 1篇 |
妇产科学 | 1篇 |
基础医学 | 146篇 |
口腔科学 | 1篇 |
临床医学 | 13篇 |
内科学 | 41篇 |
皮肤病学 | 8篇 |
神经病学 | 8篇 |
外科学 | 17篇 |
综合类 | 12篇 |
预防医学 | 38篇 |
药学 | 6篇 |
肿瘤学 | 12篇 |
出版年
2022年 | 1篇 |
2021年 | 2篇 |
2020年 | 1篇 |
2019年 | 5篇 |
2018年 | 4篇 |
2017年 | 5篇 |
2016年 | 2篇 |
2015年 | 16篇 |
2014年 | 15篇 |
2013年 | 24篇 |
2012年 | 17篇 |
2011年 | 22篇 |
2010年 | 9篇 |
2009年 | 22篇 |
2008年 | 15篇 |
2007年 | 15篇 |
2006年 | 18篇 |
2005年 | 16篇 |
2004年 | 14篇 |
2003年 | 11篇 |
2002年 | 14篇 |
2001年 | 10篇 |
2000年 | 7篇 |
1999年 | 5篇 |
1998年 | 3篇 |
1997年 | 12篇 |
1996年 | 4篇 |
1995年 | 4篇 |
1994年 | 2篇 |
1993年 | 4篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1984年 | 2篇 |
排序方式: 共有304条查询结果,搜索用时 31 毫秒
71.
Bapi Pahar Andrew A. Lackner Jeffrey D. Lifson Arpita Das David C. Montefiori 《Virology》2009,387(2):273-284
Recent HIV vaccine failures have prompted calls for more preclinical vaccine testing in non-human primates. However, similar to HIV infection of humans, developing a vaccine that protects macaques from infection following pathogenic SIVMAC251 challenge has proven difficult, and current vaccine candidates at best, only reduce viral loads after infection. Here we demonstrate that prior infection with a chimeric simian-human immunodeficiency virus (SHIV) containing an HIV envelope gene confers protection against intravenous infection with the heterologous, highly pathogenic SIVMAC251 in rhesus macaques. Although definitive immune correlates of protection were not identified, preservation and/or restoration of intestinal CD4+ memory T cells were associated with protection from challenge and control of viremia. These results suggest that protection against pathogenic lentiviral infection or disease progression is indeed possible, and may correlate with preservation of mucosal CD4+ T cells. 相似文献
72.
LISPOT与肾移植术后6个月肾功能相关,可能为肾移植受者远期预后提供信息. 相似文献
73.
Steenhard NR Kringel H Roepstorff A Thamsborg SM Jungersen G 《Parasite immunology》2007,29(10):535-538
The objective of the present study was to develop an ELISPOT method to measure parasite-specific IL-4 producing cells during experimental Ascaris suum and Trichuris suis infections in pigs. In many experimental settings it is useful to be able to measure changes in specifically induced cytokines over time at post-mRNA level; in particular, specific measurement of IL-4 is important for studies on nematodes due to the key function of IL-4 in driving the Th2 response. Two separate experiments were carried out, one with A. suum and other with T. suis infection in which we were able to measure statistically significant increases in specific IL-4 production in peripheral blood mononuclear cells over time in parallel to an increase in blood eosinophils. Furthermore, IL-4 was measured in the colon lymph node of T. suis-infected pigs. Egg excretion and worm burdens at necropsy were measured. The ELISPOT method is a valuable tool for future experimental settings as it enables repeated and parasite-specific measurement of IL-4 at protein level when investigating, for example, immunomodulatory properties of helminths. Furthermore, the method could be used to identify specific parasite antigens inducing IL-4 production. 相似文献
74.
亚低温治疗对实验性脑出血大鼠死亡率及脑组织钙含量的影响 总被引:8,自引:0,他引:8
目的本研究观察32℃亚低温对实验性脑出血大鼠24h内死亡率和脑组织钙含量的影响。方法134只大鼠分成两部分:(1)68只大鼠用于死亡率观察;(2)66只大鼠用于脑组织钙含量测定。每一部分分成假手术对照组、常温脑出血组及亚低温脑出血组。结果常温组24h内死亡率为36.67%,亚低温组为4.55%;脑组织钙含量常温组较对照组和亚低温组为高。结论亚低温治疗能显著减少实验性脑出血大鼠24h内死亡率,减少脑出血后脑组织钙含量。 相似文献
75.
The immune response in the fox (Vulpes vulpes), despite the success of the oral rabies vaccine is not well characterized, and specific immunological tools are needed. To investigate both the humoral and cellular immune response, we used ovalbumin (OVA) and cholera toxin B (CTB) as an antigenic model to set-up ELISA and ELISPOT antibodies secreting cells (ASC) assays in the fox model. Identification of antibodies that cross-react with fox immunoglobulin was performed by Western blot, and their use was adapted for both the ELISA and ELISPOT ASC assay. The humoral and cellular specific immune responses were assessed after intra-muscular or intra-nasal immunization. Intra-muscular immunization resulted in the development of both cellular and humoral anti-OVA and anti-CTB responses in peripheral blood mononuclear cells (PBMCs). Immunization via the intra-nasal route resulted in the development of a cellular and humoral response against CTB in PBMCs. This immune response was confirmed using splenocytes from immunized animals by ELISPOT assay at euthanasia. Females immunized via the intra-nasal route developed specific anti-CTB IgM, IgA and IgG in vaginal fluids after the initial boost (day 26) showing that mucosal immunization produces a vaginal immune response in foxes. These immunological tools developed here are now available to be adapted to other antigenic models to facilitate further immune studies in foxes. 相似文献
76.
Todd RW Roberts S Mann CH Luesley DM Gallimore PH Steele JC 《International journal of cancer. Journal international du cancer》2004,108(6):857-862
Human papillomavirus (HPV)-associated vulvar intraepithelial neoplasia (VIN) has serious sequelae for the sufferer. Current treatments are associated with poor response and high relapse rates. The development of HPV-specific T cell immunotherapies offers a new approach to treatment. This will require a detailed understanding of the spectrum of T cell responses induced by HPV antigens, and how effectively viral antigens can be accessed by the immune system. We have investigated the frequency and spectrum of HPV16-specific CD8+ T cell responses to three HPV16 antigens in 9 women with high grade VIN (VIN3). CD4-depleted populations of responder cells were screened against overlapping 30-35mer peptides covering the sequences of HPV16 E6, E7 and E4 using ELISPOT assays of IFN-gamma release. We demonstrated CD8+ T cell reactivity to one or more of the proteins in 6 of 9 patient samples. All 6 of these responders recognised peptides covering the E7 protein, 3 of 9 women responded to E6 peptides, but no reactivity was seen to E4. Our results suggest that HPV16-specific cytotoxic T cells (CTLs) are relatively common in women with persistent VIN3. The HPV-specific CTL response, however, seems to be ineffective. There is some evidence that there are problems associated with the processing and presentation of HPV antigens by the infected vulvar epithelium. It will be crucial to address this in the design of any T cell based therapy for HPV-associated VIN and vulval cancer. 相似文献
77.
Prolonged cold-preservation of nerve allografts 总被引:5,自引:0,他引:5
The goal of this study was to determine the effect of varying durations of cold-preservation on the immunogenicity of nerve allografts and their subsequent ability to facilitate neuroregeneration across a short nerve gap. Allografts preserved for 1, 4, and 7 weeks were compared to untreated allografts and isografts. There was a shift from an interferon-gamma-producing cellular response (untreated allografts) to an absence of response (7-week cold-preserved allografts and isografts). There were no detectable alloantibodies by flow cytometry. Histomorphometry distal to the graft showed robust regeneration in the isograft and 7-week cold-preserved groups when compared to the untreated allograft group. Increasing duration of cold-preservation diminished the cellular immune response. This cold-preservation does not preclude subsequent nerve regeneration across a short nerve graft. Prolonged cold-preservation of nerve allograft tissue could serve as a means to produce unlimited graft material for use in peripheral nerve reconstruction. 相似文献
78.
Gonzalez AM Jaimes MC Cajiao I Rojas OL Cohen J Pothier P Kohli E Butcher EC Greenberg HB Angel J Franco MA 《Virology》2003,305(1):93-105
In vivo replication of rotaviruses is generally limited to enterocytes. Because of this restriction, most blood circulating rotavirus-specific B cells are hypothesized to originate in Peyer's patches and should express the intestinal homing receptor alpha4beta7. To test this hypothesis in humans, we used a flow cytometry assay that identifies antigen-activated (IgD-) B cells (CD19+) that express surface rotavirus-specific immunoglobulin. With this assay we could detect rotavirus-specific B cells in both children and adults with an acute rotavirus (RV) infection. Staining with an anti-alpha4beta7 monoclonal antibody, we could determine that B cells that express rotavirus-specific surface immunoglobulin predominantly express alpha4beta7. The response of rotavirus-specific antibody-secreting cells in the peripheral blood of children and adults with acute rotavirus infection was also studied by ELISPOT. The antibody-secreting cells of children were mainly of the IgM isotype, while the antibody-secreting cells of adults were predominantly of the IgA and IgG isotype. alpha4beta7+ and alpha4beta7- subsets of peripheral blood mononuclear cells were purified using paramagnetic beads and then tested in the ELISPOT assay. Rotavirus-specific antibody-secreting cells were predominantly present in the alpha4beta7+ subpopulation. The flow cytometry assay we have described will permit future studies to characterize the phenotype of virus-specific B cells and could be useful in the study of the immunogenicity and protective efficacy of RV vaccines and the identification of markers of protective immunity. 相似文献
79.
Accuracy of an immune diagnostic assay based on RD1 selected epitopes for active tuberculosis in a clinical setting: a pilot study 总被引:4,自引:0,他引:4
D. Goletti S. Carrara D. Vincenti C. Saltini E. Busi Rizzi V. Schininà G. Ippolito M. Amicosante E. Girardi 《Clinical microbiology and infection》2006,12(6):544-550
A previous case-control study reported that an in-vitro interferon (IFN)-γ response to early secreted antigenic target (ESAT)-6 selected peptides was associated with active tuberculosis (A-TB). The objective of the present pilot study was to evaluate the diagnostic accuracy of this assay for TB disease in a clinical setting. An IFN-γ ELISPOT assay was performed on samples from patients with suspected A-TB using two peptides selected from ESAT-6 protein and three peptides selected from culture filtrate 10 (CFP-10) proteins. The results were compared with those obtained by two commercially available assays approved for diagnosis of TB infection (T SPOT-TB and QuantiFERON-TB Gold) which use ESAT-6/CFP-10 (RD1) overlapping peptides. Sensitivity to the RD1 selected peptides was 70% (positive for 16 of 23 patients with microbiologically diagnosed A-TB) and specificity was 91% (positive for three of 32 controls). In contrast, the sensitivity and specificity were 91%and 59%, respectively, for T SPOT-TB, and were 83% and 59%, respectively, for QuantiFERON-TB Gold. The RD1 selected peptides assay had the highest diagnostic odds ratio for A-TB. Thus, the results suggest that an assay based on RD1 selected peptides has a higher diagnostic accuracy for A-TB in a clinical setting compared with commercially available assays based on RD1 overlapping peptides. 相似文献
80.
Insights into the role of host genetic and T-cell factors in resistance to HIV transmission from studies of highly HIV-exposed Thais 总被引:3,自引:0,他引:3
Studies of resistance to HIV-1 transmission are likely to be valuable for the design of vaccines and other efforts to prevent
HIV. Here, we review the T-cell and genetic factors associated with resistance to HIV-1 transmission in studies of highly
exposed but persistently seronegative (HEPS) women from northern Thailand. Women were enrolled in two sex-worker studies and
in a discordant couple study. We performed Cr51 cytotoxic T lymphocyte (CTL), interferon-γ (IFN-γ) ELISPOT, and proliferation assays as well as genetic studies, including
HLA-class I typing. CTL and ELISPOT studies showed a skewing of T-cell responses to conserved HIV-1 proteins in HEPS, but
not in HIV-1-seropositive women. T-cell responses were extremely long-lived in some HEPS women. In the two sex-worker studies,
HLA-A11 was associated with resistance to HIV-1 transmission. These data provide promise for the ability of CTL to control
HIV and emphasize the importance of developing HIV vaccines that stimulate strong, long-lasting T-cell responses. 相似文献