全文获取类型
收费全文 | 91篇 |
免费 | 20篇 |
出版年
2021年 | 10篇 |
2018年 | 1篇 |
2016年 | 6篇 |
2015年 | 3篇 |
2014年 | 7篇 |
2013年 | 5篇 |
2012年 | 12篇 |
2011年 | 8篇 |
2010年 | 7篇 |
2009年 | 2篇 |
2008年 | 5篇 |
2007年 | 2篇 |
2006年 | 2篇 |
2005年 | 6篇 |
2004年 | 4篇 |
2003年 | 6篇 |
2002年 | 3篇 |
2001年 | 2篇 |
2000年 | 1篇 |
1999年 | 1篇 |
1998年 | 5篇 |
1995年 | 2篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1986年 | 1篇 |
1983年 | 1篇 |
1980年 | 1篇 |
1977年 | 3篇 |
1974年 | 1篇 |
1971年 | 1篇 |
1970年 | 1篇 |
排序方式: 共有111条查询结果,搜索用时 93 毫秒
21.
In vivo electroporation (EP) has been shown to augment the immunogenicity of plasmid DNA vaccines, but its mechanism of action has not been fully characterized. In this study, we show that in vivo EP augmented cellular and humoral immune responses to a human immunodeficiency virus type 1 Env DNA vaccine in mice and allowed a 10-fold reduction in vaccine dose. This enhancement was durable for over 6 months, and re-exposure to antigen resulted in anamnestic effector and central memory CD8(+) T-lymphocyte responses. Interestingly, in vivo EP also recruited large mixed cellular inflammatory infiltrates to the site of inoculation. These infiltrates contained 45-fold-increased numbers of macrophages and 77-fold-increased numbers of dendritic cells as well as 2- to 6-fold-increased numbers of B and T lymphocytes compared to infiltrates following DNA vaccination alone. These data suggest that recruiting inflammatory cells, including antigen-presenting cells (APCs), to the site of antigen production substantially improves the immunogenicity of DNA vaccines. Combining in vivo EP with plasmid chemokine adjuvants that similarly recruited APCs to the injection site, however, did not result in synergy. 相似文献
22.
Waddington SN McVey JH Bhella D Parker AL Barker K Atoda H Pink R Buckley SM Greig JA Denby L Custers J Morita T Francischetti IM Monteiro RQ Barouch DH van Rooijen N Napoli C Havenga MJ Nicklin SA Baker AH 《Cell》2008,132(3):397-409
Adenoviruses are used extensively as gene transfer agents, both experimentally and clinically. However, targeting of liver cells by adenoviruses compromises their potential efficacy. In cell culture, the adenovirus serotype 5 fiber protein engages the coxsackievirus and adenovirus receptor (CAR) to bind cells. Paradoxically, following intravascular delivery, CAR is not used for liver transduction, implicating alternate pathways. Recently, we demonstrated that coagulation factor (F)X directly binds adenovirus leading to liver infection. Here, we show that FX binds to the Ad5 hexon, not fiber, via an interaction between the FX Gla domain and hypervariable regions of the hexon surface. Binding occurs in multiple human adenovirus serotypes. Liver infection by the FX-Ad5 complex is mediated through a heparin-binding exosite in the FX serine protease domain. This study reveals an unanticipated function for hexon in mediating liver gene transfer in vivo. 相似文献
23.
Xuan He Abishek Chandrashekar Roland Zahn Frank Wegmann Jingyou Yu Noe B. Mercado Katherine McMahan Amanda J. Martinot Cesar Piedra-Mora Sidney Beecy Sarah Ducat Ronnie Chamanza Sietske Rosendahl Huber Marjolein van Heerden Leslie van der Fits Erica N. Borducchi Michelle Lifton Jinyan Liu Dan H. Barouch 《Cell》2021,184(13):3467-3473.e11
24.
25.
Yang R Sikka G Larson J Watts VL Niu X Ellis CL Miller KL Camara A Reinke C Savransky V Polotsky VY O'Donnell CP Berkowitz DE Barouch LA 《American journal of physiology. Heart and circulatory physiology》2011,300(4):H1467-H1476
Chronic intermittent hypoxia (IH) during sleep can result from obstructive sleep apnea (OSA), a disorder that is particularly prevalent in obesity. OSA is associated with high levels of circulating leptin, cardiovascular dysfunction, and dyslipidemia. Relationships between leptin and cardiovascular function in OSA and chronic IH are poorly understood. We exposed lean wild-type (WT) and obese leptin-deficient ob/ob mice to IH for 4 wk, with and without leptin infusion, and measured cardiovascular indices including aortic vascular stiffness, endothelial function, cardiac myocyte morphology, and contractile properties. At baseline, ob/ob mice had decreased vascular compliance and endothelial function vs. WT mice. We found that 4 wk of IH decreased vascular compliance and endothelial relaxation responses to acetylcholine in both WT and leptin-deficient ob/ob animals. Recombinant leptin infusion in both strains restored IH-induced vascular abnormalities toward normoxic WT levels. Cardiac myocyte morphology and function were unaltered by IH. Serum cholesterol and triglyceride levels were significantly decreased by leptin treatment in IH mice, as was hepatic stearoyl-Coenzyme A desaturase 1 expression. Taken together, these data suggest that restoring normal leptin signaling can reduce vascular stiffness, increase endothelial relaxation, and correct dyslipidemia associated with IH. 相似文献
26.
The induction of potent and durable cellular immune responses in both peripheral and mucosal tissues may be important for the development of effective vaccines against human immunodeficiency virus type 1 and other pathogens. In particular, effector responses at mucosal surfaces may be critical to respond rapidly to incoming mucosal pathogens. Here we report that intramuscular injection of nonreplicating recombinant adenovirus (rAd) vectors into rhesus monkeys induced remarkably durable simian immunodeficiency virus (SIV)-specific T lymphocyte responses that persisted for over 2 years in both peripheral blood and multiple mucosal tissues, including colorectal, duodenal, and vaginal biopsy specimens, as well as bronchoalveolar lavage fluid. In peripheral blood, SIV-specific T lymphocytes underwent the expected phenotypic evolution from effector memory T cells (T(EM)) to central memory T cells (TCM) following vaccination. In contrast, mucosal SIV-specific T lymphocytes exhibited a persistent and durable T(EM) phenotype that did not evolve over time. These data demonstrate that nonreplicating rAd vectors induce durable and widely distributed effector memory mucosal T lymphocyte responses that are phenotypically distinct from peripheral T lymphocyte responses. Vaccine-elicited T(EM) responses at mucosal surfaces may prove critical for affording protection against invading pathogens at the mucosal portals of entry. 相似文献
27.
28.
29.
Initiation of Antiviral B Cell Immunity Relies on Innate Signals from Spatially Positioned NKT Cells
Mauro Gaya Patricia Barral Marianne Burbage Shweta Aggarwal Beatriz Montaner Andrew Warren Navia Malika Aid Carlson Tsui Paula Maldonado Usha Nair Khader Ghneim Padraic G. Fallon Rafick-Pierre Sekaly Dan H. Barouch Alex K. Shalek Andreas Bruckbauer Jessica Strid Facundo D. Batista 《Cell》2018,172(3):517-533.e20
30.
Alison E. Mahan Madeleine F. Jennewein Todd Suscovich Kendall Dionne Jacquelynne Tedesco Amy W. Chung Hendrik Streeck Maria Pau Hanneke Schuitemaker Don Francis Patricia Fast Dagna Laufer Bruce D. Walker Lindsey Baden Dan H. Barouch Galit Alter 《PLoS pathogens》2016,12(3)
Antibody effector functions, such as antibody-dependent cellular cytotoxicity, complement deposition, and antibody-dependent phagocytosis, play a critical role in immunity against multiple pathogens, particularly in the absence of neutralizing activity. Two modifications to the IgG constant domain (Fc domain) regulate antibody functionality: changes in antibody subclass and changes in a single N-linked glycan located in the CH2 domain of the IgG Fc. Together, these modifications provide a specific set of instructions to the innate immune system to direct the elimination of antibody-bound antigens. While it is clear that subclass selection is actively regulated during the course of natural infection, it is unclear whether antibody glycosylation can be tuned, in a signal-specific or pathogen-specific manner. Here, we show that antibody glycosylation is determined in an antigen- and pathogen-specific manner during HIV infection. Moreover, while dramatic differences exist in bulk IgG glycosylation among individuals in distinct geographical locations, immunization is able to overcome these differences and elicit antigen-specific antibodies with similar antibody glycosylation patterns. Additionally, distinct vaccine regimens induced different antigen-specific IgG glycosylation profiles, suggesting that antibody glycosylation is not only programmable but can be manipulated via the delivery of distinct inflammatory signals during B cell priming. These data strongly suggest that the immune system naturally drives antibody glycosylation in an antigen-specific manner and highlights a promising means by which next-generation therapeutics and vaccines can harness the antiviral activity of the innate immune system via directed alterations in antibody glycosylation in vivo. 相似文献