全文获取类型
收费全文 | 267篇 |
免费 | 30篇 |
国内免费 | 1篇 |
出版年
2022年 | 7篇 |
2021年 | 11篇 |
2020年 | 4篇 |
2019年 | 3篇 |
2018年 | 3篇 |
2017年 | 2篇 |
2016年 | 9篇 |
2015年 | 12篇 |
2014年 | 14篇 |
2013年 | 14篇 |
2012年 | 15篇 |
2011年 | 12篇 |
2010年 | 12篇 |
2009年 | 6篇 |
2008年 | 7篇 |
2007年 | 16篇 |
2006年 | 15篇 |
2005年 | 8篇 |
2004年 | 14篇 |
2002年 | 10篇 |
2001年 | 7篇 |
2000年 | 2篇 |
1999年 | 2篇 |
1998年 | 2篇 |
1997年 | 2篇 |
1995年 | 4篇 |
1993年 | 6篇 |
1992年 | 6篇 |
1991年 | 3篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1987年 | 3篇 |
1986年 | 4篇 |
1985年 | 4篇 |
1984年 | 5篇 |
1983年 | 4篇 |
1982年 | 4篇 |
1981年 | 3篇 |
1980年 | 3篇 |
1977年 | 4篇 |
1976年 | 3篇 |
1975年 | 2篇 |
1974年 | 3篇 |
1972年 | 3篇 |
1968年 | 2篇 |
1967年 | 3篇 |
1965年 | 2篇 |
1962年 | 1篇 |
1960年 | 1篇 |
1939年 | 1篇 |
排序方式: 共有298条查询结果,搜索用时 31 毫秒
91.
Katharina Artinger Alexander H. Kirsch Ida Aringer Corinna Schabhüttl Alexander R. Rosenkranz Philipp Eller Elena Rho Kathrin Eller 《PloS one》2015,10(8)
Background
The spleen has been implicated in the pathogenesis of immune-complex glomerulonephritis by initiating and resolving adaptive immune responses. Thus, we aimed to evaluate the role of the spleen in experimental nephrotoxic serum nephritis (NTS).Methods
In order to accelerate the disease, animals were subjected to NTS by preimmunizing male C57BL/6J mice with rabbit IgG three days before injecting the rabbit anti-glomerular basement antiserum, or were immunized only. A group underwent splenectomy before NTS induction.Results
We observed enlargement of the spleen with a maximum at 14 days after NTS induction or immunization only. Splenectomized mice were found to develop albuminuria and renal histological changes comparable to sham-operated controls. Nevertheless, anaemia was aggravated in mice after splenectomy. During the course of NTS, we detected CD41+ megakaryocytes and Ter119+ erythroid precursor cells in the spleen of mice with NTS and of immunized mice. Ter119+Cxcr4+ cells and the binding partner Cxcl12 increased in the spleen, and decreased in the bone marrow. This was accompanied by a significant systemic increase of interferon-gamma in the serum.Conclusions
In summary, splenectomy does not influence the course of NTS per se, but is involved in concomitant anaemia. Extramedullary haematopoiesis in the spleen is probably facilitated through the migration of Cxcr4+ erythroid precursor cells from the bone marrow to the spleen via a Cxcl12 gradient and likely arises from the suppressive capacity of chronic inflammation on the bone marrow. 相似文献92.
Michael Brand Matthias Sommer Stephan Ellmann Wolfgang Wuest Matthias S. May Achim Eller Sabine Vogt Michael M. Lell Michael A. Kuefner Michael Uder 《PloS one》2015,10(5)
BackgroundRadiation exposure occurs in X-ray guided interventional procedures or computed tomography (CT) and γ-H2AX-foci are recognized to represent DNA double-strand breaks (DSBs) as a biomarker for radiation induced damage. Antioxidants may reduce the induction of γ-H2AX-foci by binding free radicals. The aim of this study was to establish a dose-effect relationship and a time-effect relationship for the individual antioxidants on DSBs in human blood lymphocytes.ResultsFor zinc, trolox and lipoic acid regardless of concentration or pre-incubation time, no significant decrease of γ-H2AX-foci was found. However, ß-carotene (15%), selenium (14%), vitamin E (12%), vitamin C (25%), NAC (43%) and Q 10 (18%) led to a significant reduction of γ-H2AX-foci at a pre-incubation time of 1 hour. The combination of different antioxidants did not have an additive effect.ConclusionAntioxidants administered prior to irradiation demonstrated the potential to reduce γ-H2AX-foci in blood lymphocytes. 相似文献
93.
94.
95.
Eller MA Slike BM Cox JH Lesho E Wang Z Currier JR Darden JM Polonis VR Vahey MT Peel S Robb ML Michael NL Marovich MA 《PloS one》2011,6(9):e24254
Background
We conducted a novel pilot study comparing different delivery routes of ALVAC-HIV (vCP205), a canarypox vaccine containing HIV gene inserts: env, gag and pol. We explored the concept that direct ex vivo targeting of human dendritic cells (DC) would enhance the immune response compared to either conventional intramuscular or intradermal injections of the vaccine alone.Methodology/Principal Findings
Healthy HIV-1 uninfected volunteers were administered ALVAC-HIV or placebo by intramuscular injection (IM), intradermal injection (ID) or subcutaneous injection (SQ) of autologous ex vivo transfected DC at months 0, 1, 3 and 6. All vaccine delivery routes were well tolerated. Binding antibodies were observed to both the ALVAC vector and HIV-1 gp160 proteins. Modest cellular responses were observed in 2/7 individuals in the DC arm and 1/8 in the IM arm as determined by IFN-γ ELISPOT. Proliferative responses were most frequent in the DC arm where 4/7 individuals had measurable responses to multiple HIV-1 antigens. Loading DC after maturation resulted in lower gene expression, but overall better responses to both HIV-1 and control antigens, and were associated with better IL-2, TNF-α and IFN-γ production.Conclusions/Significance
ALVAC-HIV delivered IM, ID or SQ with autologous ex vivo transfected DC proved to be safe. The DC arm was most immunogenic. Proliferative immune responses were readily detected with only modest cytotoxic CD8 T cell responses. Loading mature DC with the live viral vaccine induced stronger immune responses than loading immature DC, despite increased transgene expression with the latter approach. Volunteers who received the autologous vaccine loaded mature DC developed a broader and durable immune response compared to those vaccinated by conventional routes.Trial Registration
ClinicalTrials.gov NCT00013572相似文献96.
Eller MA Blom KG Gonzalez VD Eller LA Naluyima P Laeyendecker O Quinn TC Kiwanuka N Serwadda D Sewankambo NK Tasseneetrithep B Wawer MJ Gray RH Marovich MA Michael NL de Souza MS Wabwire-Mangen F Robb ML Currier JR Sandberg JK 《PloS one》2011,6(4):e18779
HIV-1 disease progression is associated with persistent immune activation. However, the nature of this association is incompletely understood. Here, we investigated immune activation in the CD4 T cell compartment of chronically HIV-1 infected individuals from Rakai, Uganda. Levels of CD4 T cell activation, assessed as co-expression of PD-1, CD38 and HLA-DR, correlated directly to viral load and inversely to CD4 count. Deeper characterization of these cells indicated an effector memory phenotype with relatively frequent expression of Ki67 despite their PD-1 expression, and levels of these cells were inversely associated with FoxP3+ regulatory T cells. We therefore use the term deregulated effector memory (DEM) cells to describe them. CD4 T cells with a DEM phenotype could be generated by antigen stimulation of recall responses in vitro. Responses against HIV-1 and CMV antigens were enriched among the DEM CD4 T cells in patients, and the diverse Vβ repertoire of DEM CD4 T cells suggested they include diverse antigen-specificities. Furthermore, the levels of DEM CD4 T cells correlated directly to soluble CD14 (sCD14) and IL-6, markers of innate immune activation, in plasma. The size of the activated DEM CD4 T cell subset was predictive of the rate of disease progression, whereas IL-6 was only weakly predictive and sCD14 was not predictive. Taken together, these results are consistent with a model where systemic innate immune activation and chronic antigen stimulation of adaptive T cell responses both play important roles in driving pathological CD4 T cell immune activation in HIV-1 disease. 相似文献
97.
98.
Robert J. McLinden Celia C. LaBranche Agnès-Laurence Chenine Victoria R. Polonis Michael A. Eller Lindsay Wieczorek Christina Ochsenbauer John C. Kappes Stephen Perfetto David C. Montefiori Nelson L. Michael Jerome H. Kim 《PloS one》2013,8(11)
Sensitive assays are needed to meaningfully assess low levels of neutralizing antibodies (NAbs) that may be important for protection against the acquisition of HIV-1 infection in vaccine recipients. The current assay of choice uses a non-lymphoid cell line (TZM-bl) that may lack sensitivity owing to over expression of CD4 and CCR5. We used transfection of a human CD4+/CXCR4+/α4β7+ T-lymphoblastoid cell line (A3.01) with a CMV IE promoter-driven CCR5neo vector to stably express CCR5. The resulting line, designated A3R5, is permissive to a wide range of CCR5-tropic circulating strains of HIV-1, including HIV-1 molecular clones containing a Tat-inducible Renilla luciferase reporter gene and expressing multiple Env subtypes. Flow cytometric analysis found CCR5 surface expression on A3R5 cells to be markedly less than TZM-bl but similar to CD3.8 stimulated PBMC. More importantly, neutralization mediated by a diverse panel of monoclonal antibodies, HIV-1 positive polyclonal sera and sCD4 was consistently greater in A3R5 compared to TZM-bl cells. The A3R5 cell line provides a novel approach to guide the development and qualification of promising new HIV-1 vaccine immunogens. 相似文献
99.
Noll GA Müller B Ernst AM Rüping B Twyman RM Prüfer D 《Applied microbiology and biotechnology》2011,89(6):1675-1682
Forisomes are remarkable protein bodies found exclusively in the phloem of the Fabaceae. When the phloem is wounded, forisomes
are converted from a condensed to a dispersed state in an ATP-independent reaction triggered by Ca2+, thereby plugging the sieve tubes and preventing the loss of photoassimilates. Potentially, forisomes are ideal biomaterials
for technical devices because the conformational changes can be replicated in vitro and are fully reversible over a large
number of cycles. However, the development of technical devices based on forisomes has been hampered by the laborious and
time-consuming process of purifying native forisomes from plants. More recently, the problem has been overcome by the production
of recombinant artificial forisomes. This is a milestone in the development of forisome-based devices, not only because large
quantities of homogeneous forisomes can be produced on demand, but also because their properties can be tailored for particular
applications. In this review, we discuss the physical and molecular properties of native and artificial forisomes, focusing
on their current applications in technical devices and potential developments in the future. 相似文献
100.
Harmful algal blooms have a severe impact on aquaculture andfishery and can be caused by toxic haptophytes and dinoflagellates.Different toxic species, which are not easy to distinguish fromtheir morphologically similar and non-toxic relatives, occurin both groups. Sequencing of the large subunit ribosomal RNAof different strains and taxonomic relatives allowed the designof a probe specific to the toxic Prymnesium parvum spp. Forthe rapid detection and enumeration of Prymnesium and Alexandriumcells in cultures and environmental samples, respectively, protocolsfor fluorescence in situ hybridization were adapted for automateddetection by a solid-phase cytometer, the ChemScan. This cytometerenables the automated counting of fluorescently labelled cellson a membrane filter and subsequently a microscopic verificationof these results by the user, because the motorized stage ofthe microscope is driven to each positive signal by the computersoftware to localize that cell on the filter. With this fastdetection method, it was possible to detect, enumerate and verifymicroalgal cells on a filter, with a detection limit of onecell per membrane filter. 相似文献