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121.
Pascale Hubert Roland Greimers Elizabeth Franzen-Detrooz Jean Doyen Pierre Delanaye Jacques Boniver Philippe Delvenne 《Cancer immunology, immunotherapy : CII》1998,47(2):81-89
Dendritic cells (DC) are the most efficient antigen presenting cells. The clinical use of DC as vectors for antitumor and
anti-infectious disease immunotherapy has been limited by their low level and accessibility in normal tissue. Substantial
numbers of DC can be generated from peripheral blood cultured in the presence of interleukin-4 (IL-4) and granulocyte/macrophage-colony-stimulating
factor (GM-CSF). We showed in this study that substantial numbers of DC can be obtained from the peripheral blood of patients
with (pre)neoplastic lesions of the uterine cervix. The procedure required relatively small blood samples (10 ml) and the
presence of 100 U/ml IL-4 and 800 U/ml GM-CSF in the culture medium. There was no significant difference in the morphology,
yield, phenotype and function of generated DC between patients with cervical (pre)neoplastic lesions and healthy individuals.
When the hematopoietic factor Flt3 ligand (Flt3L, 40 ng/ml) was added, there was an average increase in the DC population
of 26% compared to cultures with GM-CSF and IL-4 alone. Approximately 1.2 × 106 cells with the characteristics of dendritic cells could be obtained when Flt3L was included in the medium. The addition of
Flt3L did not modify the phenotypic profile of DC (HLA-DR+, CD1a+, CD4+, CD54+, CD80+, CD86+, CD40+, CD3− and CD14−). In addition, Flt3L generated functional DC capable of stimulating the proliferation of alloreactive T cells. These results
suggest that Flt3L, in association with GM-CSF and IL-4, provides an advantageous tool for the large-scale generation of DC
and that an immunotherapy based on the use of DC generated in vitro is possible in patients with (pre)neoplastic lesions of
the uterine cervix.
Received: 8 January 1998 / Accepted: 30 April 1998 相似文献
122.
123.
Design of bifunctional siRNAs: combining immunostimulation and gene-silencing in one single siRNA molecule 总被引:1,自引:0,他引:1
Active suppression of T lymphocyte activation can limit the efficacy of immune surveillance and immunotherapy. Here we have explored the possibility of designing bifunctional small interfering RNAs (siRNAs) capable of inducing innate immunity through Toll-like receptors and simultaneously inhibiting the expression of immunosuppressive factors. Using interleukin (IL) 10 as a model, we found that liposomal delivery of IL10 siRNAs could efficiently activate the expression of cytokines (e.g. TNF-alpha, IL6, and IL12) and interferons (e.g. IFN-alpha) in peripheral blood mononuclear cells (PBMCs) and immature monocyte-derived dendritic cells (iMoDCs). Moreover, the designed siRNAs inhibited IL10 gene expression. Transfection of iMoDCs with either chemically or in vitro transcribed IL10 siRNAs induced their differentiation into mature MoDCs (mMoDCs) characterized by the expression of costimulatory molecules CD80/CD86 and the chemokine receptor CCR7. Lipid delivery of either chemically synthesized or T7-transcribed immunostimulatory siRNAs induced cytokine production. However, in contrast to chemically synthesized siRNAs, electroporation of in vitro transcribed siRNAs also induced cytokine production in iMoDCs. Interestingly, IL10 siRNA-transfected iMoDCs were capable for enhancing the response of allogeneic T cells, providing support for the rational design of bifunctional siRNAs as immune modulating therapy. 相似文献
124.
Xia CQ Peng R Annamalai M Clare-Salzler MJ 《Biochemical and biophysical research communications》2007,352(4):960-965
Mature dendritic cells (mDCs) undergo "exhaustion" in producing cytokines. Nevertheless, whether this "exhaustion" of mDCs is selective to certain cytokines, or whether mDCs have specific cytokine-producing profiles has yet to be defined. Herein, we investigated the cytokine production in vitro by immature DCs (iDCs) and LPS-induced mDCs. Compared to iDCs, mDCs produced comparable levels of IL-6 and TNF-alpha. Strikingly, mDCs produced significantly higher IFN-gamma and IL-10. IL-12 production of mDCs was suppressed. Kinetic studies of the responses of iDCs and mDCs to LPS or CD40L showed that mDCs acquired progressively heightened activity in producing IFN-gamma and IL-10. TNF-alpha-, IL-6-producing capability of mDCs was maintained. Nevertheless, IL-12 production by mDCs was not recovered at any time point. Mature DCs were potent in priming both Th1 and Th2 cells. In conclusion, upon maturation, DCs are reprogrammed with a distinct cytokine-secreting profile, which may play an important role in regulating T cell functions. 相似文献
125.
Ishikawa R Katoh K Takahashi A Xie C Oseki K Watanabe M Igarashi M Nakamura A Kohama K 《Biochemical and biophysical research communications》2007,359(2):398-401
Drebrin-A is an actin-binding protein localized in the dendritic spines of mature neurons, and has been suggested to affect spine morphology [K. Hayashi, T. Shirao, Change in the shape of dendritic spines caused by overexpression of drebrin in cultured cortical neurons, J. Neurosci. 19 (1999) 3918-3925]. However, no biochemical analysis of drebrin-A has yet been reported. In this study, we purified drebrin-A using a bacterial expression system, and characterized it in vitro. Drebrin-A bound to actin filaments with a stoichiometry of one drebrin molecule to 5-6 actin molecules. Furthermore, drebrin-A decreased the Mg-ATPase activity of myosin V. In vitro motility assay revealed that the attachment of F-actin to glass surface coated with myosin-V was decreased by drebrin-A, but once F-actin attached to the surface, the sliding speed of F-actin was unaffected by the presence of drebrin A. These findings suggest that drebrin-A may affect spine dynamics, vesicle transport, and other myosin-V-driven motility in neurons through attenuating the interaction between actin and myosin-V. 相似文献
126.
Heiko Zimmermann Rolf Hagedorn Ekkehard Richter Günter Fuhr 《European biophysics journal : EBJ》1999,28(6):516-525
Migrating adherent cells release material onto artificial substrates like glass and silicon while moving. Traces of mouse
fibroblasts (L929) have been visualised by atomic force microscopy (AFM). “Non-contact” mode AFM in a liquid environment can
extract topographic information from these traces. This dynamic mode allows the study of these soft structures without damage
or compression. The AFM images show crossing and branching networks (with specific angles of branching), structured patches,
nodular elements, linear elements with irregular height and other features. Fourier analysis of segment spacing in the strands
is presented. These spatial features of fibroblast traces are strong indications that actin linked to structural proteins
is involved in the formation of cell traces. We also give methods for trace preparation and undistorted imaging and discuss
further perspectives.
Received: 11 January 1999 / Revised version: 1 April 1999 / Accepted: 8 April 1999 相似文献
127.
Homing of intravenously and intralymphatically injected human dendritic cells generated in vitro from CD34+ hematopoietic progenitor cells 总被引:6,自引:0,他引:6
Andreas Mackensen Thomas Krause Uli Blum Peter Uhrmeister Roland Mertelsmann Albrecht Lindemann 《Cancer immunology, immunotherapy : CII》1999,48(2-3):118-122
Dendritic cells (DC) are professional antigen-presenting cells that can be generated in vitro from CD34+ peripheral blood progenitor cells by recombinant cytokines. These cells have potential implications for immunotherapeutic
approaches in the treatment of cancer and other diseases. Physiologically, immature DC in the periphery capture and process
antigens, then mature to interdigitating DC and migrate to lymphoid organs, where they activate lymphocytes. However, it is
not known if DC generated in vitro have the capacity to traffic in vivo to the lymphoid tissues, such as spleen and lymph
nodes. We have investigated whether human radiolabeled DC differentiated in vitro migrate and localize to lymphoid tissues
after intravenous and intralymphatic injection. The distribution and localization of the DC were evaluated in five patients
with malignant melanoma using serial whole-body gamma camera imaging. Intravenously infused DC demonstrated transient lung
uptake followed by localization in the spleen and liver for at least 7 days. DC injected into a lymphatic vessel at the dorsal
foot were rapidly detected in the draining lymph nodes where they remained for more than 24 h. These data suggest that DC
differentiated in vitro localize preferentially to lymphoid tissue, where they could induce specific immune responses.
Received: 28 January 1999 / Accepted: 4 March 1999 相似文献
128.
王佃亮 《中国生物工程杂志》2016,36(7):127-133
细胞药物制备的质量直接关系到细胞治疗的效果。由于细胞治疗所用细胞是具有生物学效应的,细胞药物的制备技术和应用方案具有多样性、复杂性和特殊性,不像一般生物药物那样有统一的制作标准。细胞药物的制备过程主要包括供者筛查、供者检测、采集、加工、分离纯化、储存等,以造血干细胞、间充质干细胞、肝细胞及树突状细胞为例对其进行简要介绍。 相似文献
129.
Juliana Moreira de Sousa-Canavez Cristina de Oliveira Massoco Elaine Cristina Corneta Luiz Heraldo Camara-Lopes 《Cellular immunology》2009,259(1):41-48
All-trans-retinoic acid (atRA) appears to affect Th1-Th2 differentiation and its effects on immune responses might also be mediated by dendritic cell (DC). Nonetheless, studies have been showing contradictory results since was observed either induction or inhibition of DC differentiation. Our aim was to investigate atRA action on human monocyte derived DC differentiation. For this purpose we tested pharmacological and physiological doses of atRA with or without cytokines. Cell phenotypes were analyzed by flow cytometry and function was investigated by phagocytosis and respiratory burst. DC, positive control group, was differentiated with GM-CSF and IL-4 and maturated with TNF-α. We demonstrated that atRA effects depend on the dose used as pharmacological doses inhibited expression of all phenotypic markers tested while a physiological dose caused cell differentiation. However, atRA combined or not with cytokines did not promote DC differentiation. In fact, atRA was detrimental on IL-4 property as a DC inductor. 相似文献
130.