全文获取类型
收费全文 | 132篇 |
免费 | 12篇 |
出版年
2017年 | 1篇 |
2016年 | 5篇 |
2015年 | 7篇 |
2014年 | 5篇 |
2013年 | 7篇 |
2012年 | 6篇 |
2011年 | 3篇 |
2010年 | 4篇 |
2009年 | 7篇 |
2008年 | 11篇 |
2007年 | 7篇 |
2006年 | 4篇 |
2005年 | 4篇 |
2004年 | 6篇 |
2003年 | 3篇 |
2002年 | 4篇 |
2001年 | 5篇 |
2000年 | 7篇 |
1999年 | 5篇 |
1998年 | 3篇 |
1997年 | 2篇 |
1995年 | 3篇 |
1993年 | 2篇 |
1992年 | 5篇 |
1991年 | 2篇 |
1990年 | 3篇 |
1989年 | 3篇 |
1988年 | 5篇 |
1987年 | 3篇 |
1983年 | 3篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1979年 | 1篇 |
1976年 | 1篇 |
1926年 | 1篇 |
1918年 | 1篇 |
1903年 | 1篇 |
1900年 | 1篇 |
1891年 | 1篇 |
排序方式: 共有144条查询结果,搜索用时 15 毫秒
61.
John E. Blundell Clare L. Lawton Jason CG Halford 《Obesity (Silver Spring, Md.)》1995,3(Z4):471S-476S
There is an intimate relationship between nutritional intake (eating) and serotonin activity. Experimental manipulations (mainly neuropharmacological) of serotonin influence the pattern of eating behavior, subjective feelings of appetite motivation, and the response to nutritional challenges. Similarly, nutritional manipulations (food restriction, dieting, or altered nutrient supply) change the sensitivity of the serotonin network. Traditionally, serotonin has been linked to the macronutrient carbohydrate via the intermediary step of plasma amino acid ratios. However, it has also been demonstrated that 5-HT drugs will reduce energy intake and reverse body weight gain in rats exposed to weight increasing high fat diets. 5-HT drugs can also reduce food intake and block weight gain of rats on a high fat cafeteria diet. Some diet selection studies in rats indicate that the most prominent reduction of macronutrient intake is for fat. These data indicate that 5-HT activity can bring about a reduction in fat consumption. In turn, different types of dietary fat can alter brain 5-HT activity. In human studies the methodology of food choice experiments has often precluded the detection of an effect of 5-HT manipulation on fat intake. However, there is evidence that in obese and lean subjects some 5-HT drugs can readily reduce the intake of high fat foods. Data also suggest that 5-HT activation can lead to a selective avoidance of fat in the diet. These effects of 5-HT on the intake of dietary fat may involve a pre-absorptive mechanism and there is evidence that 5-HT is linked to cholecystokinin and enterostatin. These proposals have theoretical and practical implications and suggest possible strategies to intensify or advance fat-induced satiety signals. 相似文献
62.
IL-4 decreases Fc gamma R membrane expression and Fc gamma R-mediated cytotoxic activity of human monocytes 总被引:6,自引:0,他引:6
A A te Velde R J Huijbens J E de Vries C G Figdor 《Journal of immunology (Baltimore, Md. : 1950)》1990,144(8):3046-3051
Monocytes can express three classes of FcR for IgG: Fc gamma RI, Fc gamma RII, and Fc gamma RIII (CD64, CD32, and CD16, respectively) of which the Fc gamma RIII is expressed after prolonged culture. Fc gamma R expression is regulated by IFN-gamma. Because IFN-gamma and IL-4 have antagonistic effects on the expression of the FcR for IgE on human monocytes, we studied the effect of IL-4 on Fc gamma R expression and function. We show that IL-4 down-regulates Fc gamma RI, Fc gamma RII, and Fc gamma RIII expression of cultured monocytes and inhibits IFN-gamma enhanced Fc gamma RI expression. Exposure of monocytes to IL-4 for 40 h resulted in a dose-dependent decrease of the expression of all three Fc gamma R that persisted throughout the whole culture period (7 days). Anti-IL-4 antibodies completely reversed the IL-4 effect. In addition the impaired Fc gamma R expression correlated directly with reduced Fc gamma R-mediated function because monocytes cultured in the presence of IL-4 have a reduced capacity to lyse human E opsonized with human IgG anti-D or mouse antiglycophorin A antibodies. These observations, together with the previous finding that IL-4 induces Fc epsilon RIIb expression on monocytes, indicate that IL-4 and IFN-gamma may control the Fc gamma R-mediated immune response by differentially regulating Fc gamma R expression. 相似文献
63.
64.
Alex L Pereira Thiago N Silva Ana CMM Gomes Ana CG Araújo Loreny G Giugliano 《BMC microbiology》2010,10(1):57
Background
Enteroaggregative Escherichia coli (EAEC) are enteropathogenic strains identified by the aggregative adhesion (AA) pattern that share the capability to form biofilms. Citrobacter freundii is classically considered as an indigenous intestinal species that is sporadically associated with diarrhea. 相似文献65.
Tel J Hato SV Torensma R Buschow SI Figdor CG Lesterhuis WJ de Vries IJ 《Cancer immunology, immunotherapy : CII》2012,61(7):1101-1111
It has become evident that the tumor microenvironment plays a pivotal role in the maintenance of cancerous growth. One of the acquired functions of the tumor microenvironment is the suppression of immune responses. Indeed, blocking the inhibitory pathways operational in the microenvironment results in enhanced T-cell-dependent, anti-tumor immunity. Chemotherapeutic drugs not only directly kill tumor cells but also shape the tumor microenvironment and potentiate anti-tumor immunity. Here, we demonstrate that the chemotherapeutic compound oxaliplatin acts as a double-edged sword. Besides killing tumor cells, oxaliplatin bolsters immunosuppressive pathways, resulting in decreased activation of T cells by human plasmacytoid dendritic cells (pDCs). Exposure to oxaliplatin markedly increased expression of the T-cell inhibitory molecule programmed death receptor-ligand 1 (PD-L1) on human pDCs and also TLR9-induced IFNα secretion. Furthermore, oxaliplatin decreased TLR-induced STAT1 and STAT3 expression, and NF-κB-mediated responses. The oxaliplatin induced upregulation of PD-L1 and downregulation of costimulatory molecules CD80 and CD86 resulted in decreased T-cell proliferation. Our results demonstrate that platinum-based anticancer drugs adapt TLR-induced signaling in human pDCs and myeloid DCs (mDCs), thereby downgrading their immunostimulatory potential. 相似文献
66.
María F. García-Parajó Bärbel I. de Bakker Marjolein Koopman Alessandra Cambi Frank de Lange Carl G. Figdor Niek F. van Hulst 《NanoBioTechnology》2005,1(1):113-120
The ability to study the structure and function of cell membranes and membrane components is fundamental to understanding
cellular processes. This requires the use of methods capable of resolving structures with nanometer-scale resolution in intact
or living cells. Although fluorescence microscopy has proven to be an extremely versatile tool in cell biology, its diffraction-limited
resolution prevents the investigation of membrane compartmentalization at the nanometer scale. Near-field scanning optical
microscopy (NSOM) is a relatively unexplored technique that combines both enhanced spatial resolution of probing microscopes
and simultaneous measurement of topographic and optical signals. Because of the very small nearfield excitation volume, background
fluorescence from the cytoplasm is effectively reduced, enabling the visualization of nano-scale domains on the cell membrane
with single molecule detection sensitivity at physiologically relevant packing densities. In this article we discuss technological
aspects concerning the implementation of NSOM for cell membrane studies and illustrate its unique advantages in terms of spatial
resolution, background suppression, sensitivity, and surface specificity for the study of protein clustering at the cell membrane.
Furthermore, we demonstrate reliable operation under physiological conditions, without compromising resolution or sensitivity,
opening the road toward truly live cell imaging with unprecedented detail and accuracy. 相似文献
67.
68.
Boullart AC Aarntzen EH Verdijk P Jacobs JF Schuurhuis DH Benitez-Ribas D Schreibelt G van de Rakt MW Scharenborg NM de Boer A Kramer M Figdor CG Punt CJ Adema GJ de Vries IJ 《Cancer immunology, immunotherapy : CII》2008,57(11):1589-1597
Dendritic cells (DC) are professional antigen-presenting cells of the immune system that play a key role in regulating T cell-based immunity. In vivo, the capacity of DC to activate T cells depends on their ability to migrate to the T cell areas of lymph nodes as well as on their maturation state. Depending on their cytokine-secreting profile, DC are able to skew the immune response in a specific direction. In particular, IL-12p70 producing DC drive T cells towards a T helper 1 type response. A serious disadvantage of current clinical grade ex vivo generated monocyte-derived DC is the poor IL-12p70 production. We have investigated the effects of Toll-like receptor (TLR)-mediated maturation on ex vivo generated human monocyte-derived DC. We demonstrate that in contrast to cytokine-matured DC, DC matured with poly(I:C) (TLR3 ligand) and/or R848 (TLR7/8 ligand) are able to produce vast amounts of IL-12p70, but exhibit a reduced migratory capacity. The addition of prostaglandin E(2) (PGE(2)) improved the migratory capacity of TLR-ligand matured DC while maintaining their IL-12p70 production upon T cell encounter. We propose a novel clinical grade maturation protocol in which TLR ligands poly(I:C) and R848 are combined with PGE(2) to generate DC with both high migratory capacity and IL-12p70 production upon T cell encounter. 相似文献
69.
The dendritic cell-specific adhesion receptor DC-SIGN internalizes antigen for presentation to T cells 总被引:34,自引:0,他引:34
Engering A Geijtenbeek TB van Vliet SJ Wijers M van Liempt E Demaurex N Lanzavecchia A Fransen J Figdor CG Piguet V van Kooyk Y 《Journal of immunology (Baltimore, Md. : 1950)》2002,168(5):2118-2126
Dendritic cells (DCs) capture Ags or viruses in peripheral tissue to transport them to lymphoid organs to induce cellular T cell responses. Recently, a DC-specific C-type lectin was identified, DC-specific ICAM-grabbing non-integrin (DC-SIGN), that functions as cell adhesion receptor mediating both DC migration and T cell activation. DC-SIGN also functions as an HIV-1R that captures HIVgp120 and facilitates DC-induced HIV transmission of T cells. Internalization motifs in the cytoplasmic tail of DC-SIGN hint to a function of DC-SIGN as endocytic receptor. In this study we demonstrate that on DCs DC-SIGN is rapidly internalized upon binding of soluble ligand. Mutating a putative internalization motif in the cytoplasmic tail reduces ligand-induced internalization. Detailed analysis using ratio fluorescence imaging and electron microscopy showed that DC-SIGN-ligand complexes are targeted to late endosomes/lysosomes. Moreover, ligands internalized by DC-SIGN are efficiently processed and presented to CD4+ T cells. The distinct pattern of expression of C-type lectins on DCs in situ and their nonoverlapping Ag recognition profile hint to selective functions of these receptors to allow a DC to recognize a wide variety of Ags and to process these to induce T cell activation. These data point to a novel function of the adhesion receptor DC-SIGN as an efficient DC-specific Ag receptor that can be used as a target to induce viral and antitumor immunity. 相似文献
70.