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排序方式: 共有2233条查询结果,搜索用时 140 毫秒
1.
Apoptosis pathways in cancer and cancer therapy   总被引:30,自引:0,他引:30  
Activation of apoptosis pathways is a key mechanism by which cytotoxic drugs kill tumor cells. Also immunotherapy of tumors requires an apoptosis sensitive phenotype of target cells. Defects in apoptosis signalling contribute to resistance of tumors. Activation of apoptosis signalling following treatment with cytotoxic drugs has been shown to lead to activation of the mitochondrial (intrinsic) pathway of apoptosis. In addition, signalling through the death receptor (extrinsic) pathways, contributes to sensitivity of tumor cells towards cytotoxic treatment. Both pathways converge finally at the level of activation of caspases, the effector molecules in most forms of cell death. In addition to classical apoptosis, non-apoptotic modes of cell death have recently been identified. Mechanisms to overcome apoptosis resistance include direct targeting of antiapoptotic molecules expressed in tumors as well as re-sensitization of previously resistant tumor cells by re-expression of caspases and counteracting apoptotis inhibitory molecules such as Bcl-2 and molecules of the IAP family of endogenous caspase inhibitors. Molecular insights into regulation of apoptosis and defects in apoptosis signalling in tumor cells will provide novel approaches to define sensitivity or resistance of tumor cells towards antitumor therapy and provide new targets for rational therapeutic interventions for future therapeutic strategies.This work was presented at the first Cancer Immunology and Immunotherapy Summer School, 8–13 September 2003, Ionian Village, Bartholomeio, Peloponnese, Greece.  相似文献
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Photoluminescent semiconductor quantum dots (QDs) are novel nanometer-size probes that have found bioimaging. Here we imaged a cell line of mouse lymphocytes. QDs were actively taken into the target cells by endocytotic pathways. The fluorescence of QDs held in the endosomes could be studied for more than a week and remained stable luminescence against cell activation induced by concanavalin A, phytohemagglutinin, phorbol myristate acetate, and calcium ionophore A23187. These results suggested that QD-labeling was stable and did not affect either cell activation or cell function. When QD-labeled cells were intravenously injected into mouse, they remained in the peripheral blood in a concentration of approximately 10% up to 5 days after injection using both fluorescence microscopy and flow cytometry. In addition, approximately 20% of QDs were detected in the kidneys, liver, lung, and spleen and could still be observed 7 days after injection. These results suggested that fluorescent probes of QDs might be useful as bioimaging tools for tracing target cells over the period of a week in vivo.  相似文献
3.
Superantigen-based tumor therapy: in vivo activation of cytotoxic T cells   总被引:23,自引:0,他引:23  
We have recently demonstrated that the superantigen staphylococcal enterotoxin A (SEA) targets in vitro activated cytotoxic T lymphocytes against tumor cells expressing major histocompatibility complex (MHC) class II antigens. In this report we analyze the use of SEA as an immunoactivator in vivo. Treatment of mice with SEA activated a fraction of CD3+ T cells apparently as a function of their T cell receptor V expression. SEA induced interleukin-2 receptor expression and proliferation in both CD4+ and CD8+ T cells. This proliferative response was dose-dependent (0.1 – 100 µg/mouse), peaked during day 1 after treatment and declined to background levels within 4 days. The cytotoxic response, measured as cytotoxicity to SEA-coated MHC class II+ target cells (staphylococcal-enterotoxin-dependent cell-mediated cytotoxicity, SDCC), was maximal at a dosage of 1 µg SEA/mouse. The SDCC was confined to the CD8+ T cell compartment, peaked 2 days after treatment and declined to background levels within 4 days. A second injection of SEA on day 5 after the first SEA treatment resulted in SDCC function with kinetics and magnitude identical to that seen after one injection. These results pave the way for the use of SEA in the treatment of MHC class II+ tumors.  相似文献
4.
ULBP4 is a novel ligand for human NKG2D   总被引:21,自引:0,他引:21  
The ULBPs are a family of MHC class I-related molecules. We have previously shown that ULBPs 1, 2, and 3 are functional ligands of the NKG2D/DAP10 receptor complex on human natural killer (NK) cells. Here, we describe a new member of the ULBP family, ULBP4, which contains predicted transmembrane and cytoplasmic domains, unlike the other ULBPs, which are GPI-linked proteins. Transduction of ULBP4 into EL4 cells confers the ability to bind recombinant NKG2D and mediates increased cytotoxic activity by human NK cells, consistent with the role of ULBPs as ligands for the NKG2D/DAP10 activating receptors. Tissue expression of ULBP4 differs from other members of the family, in that it is expressed predominantly in the skin.  相似文献
5.
Immune modulation by mesenchymal stem cells   总被引:18,自引:0,他引:18  
Mesenchymal stem cells (MSCs) have been shown to suppress activation of T cells both in vivo and in vitro. In vivo, this may be a way for the body to maintain homeostasis and inhibit immune activation in distinct compartments, such as the bone marrow and the interface between mother and fetus. MSCs modulate the immune function of the major cell populations involved in alloantigen recognition and elimination, including antigen presenting cells, T cells, and natural killer cells. The molecular mechanism that mediates the immunosuppressive effect of MSCs is not completely understood.  相似文献
6.
MYOC encoding a 55kDa secretory glycoprotein named myocilin is closely linked to primary open-angle glaucoma (POAG). To understand a role played by MYOC in glaucoma, we examined the cellular fate of various mutant myocilins that were adenovirally expressed in human trabecular meshwork cells. Most myocilins with mutations such as G364V, Q368X, K423E, Y437H, and I477N were intrinsically stable, and appeared to have interactions with wild-type myocilin but not with stromelysin and thereby selectively inhibited the secretion of the former protein. The myocilins expressed were identified to be concentrated into fine punctate aggregates in endoplasmic reticulum, but never developed into the formation of aggresomes. In endoplasmic reticulum, the accumulation of the myocilins resulted in the upregulation of 78kDa glucose-regulated protein and protein disulfide isomerase. In addition, the expression of the myocilins led to deformed cellular morphology and diminished cell proliferation, an effect postulated to result in the dysfunction of trabecular cells that could be a cause of glaucoma. Therefore, our results support the statement that gain of function rather than haploinsufficiency is a critical mechanism for POAG in individuals with mutations on MYOC.  相似文献
7.
Standard allogeneic stem cell transplantation (alloSCT) has provided a cure for chronic myeloid leukaemia (CML) over the last 25 years, but is only an option for a minority of patients. It was hoped that the introduction of imatinib mesylate (IM), a specific tyrosine kinase inhibitor that targets the Bcr-Abl oncogene product, would provide long-term remission or even cure for those patients without a donor, but studies have shown that IM does not eliminate leukaemic stem cells in CML patients. To overcome this problem of molecular persistence, research is underway to combine reduced intensity stem cell transplant or non-donor-dependent immunotherapies with IM with the aim of increasing cure rate, reducing toxicity and improving quality of life. The alternative approach is to combine IM or second-generation agents with other novel drugs that interrupt key signalling pathways activated by Bcr-Abl. This article will focus on the latest immunotherapy and molecularly targeted therapeutic options in CML and how they may be combined to improve the outcome for CML patients in the future.  相似文献
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海南近海30株抗B16细胞活性放线菌的16S rDNA多样性分析   总被引:15,自引:1,他引:14       下载免费PDF全文
从海南近海 ,包括文昌红树林、海口红树林以及洋浦港等地采集样品 ,经苯酚、SDS、加热等预处理 ,稀释涂布麦芽汁_酵母膏琼脂 (YE)、淀粉酪素琼脂 (SC)、葡萄糖天冬氨酸琼脂 (GA) ,或者直接将样品稀释涂布加有重铬酸钾的高氏一号琼脂 (Gause)和麦芽汁_酵母膏琼脂等进行平板分离。共获得 35 4株放线菌 ,其中有 76株具有不同程度的抗B16细胞毒活性。比较发现加热预处理法和重铬酸钾选择培养法对于广泛分离筛选抗肿瘤活性放线菌不失为一种快速、简便、行之有效的方法。YE、Gause培养基无论在分离到的放线菌总数 ,还是细胞毒活性菌株的比例上都显示了良好的效果。对 30株具有较强抗B16细胞活性的链霉菌进行了扩增性 16SrDNA限制性酶切片段多样性分析 (16SARDRA) ,表明这 30株链霉菌之间有较大的基因差异性。 0 5 0 6 4 2、0 6 0 386和 0 6 0 5 2 4等 3株菌序列分析进一步证明这 3株菌属于链霉菌属 ,其中菌株 0 5 0 6 4 2与其亲缘关系最近的Streptomycescattleya的相似性仅为 95 % ,因此可能是一个新种。  相似文献
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