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991.
Coxsackievirus B3-induced apoptosis and caspase-3   总被引:11,自引:0,他引:11  
Yuan JP  Zhao W  Wang HT  Wu KY  Li T  Guo XK  Tong SQ 《Cell research》2003,13(3):203-209
  相似文献   
992.
The enigmatic role of angiopoietin-1 in tumor angiogenesis   总被引:13,自引:0,他引:13  
A tumor vasculature is highly unstable and immature, characterized by a high proliferation rate of endothelial cells, hyper-permeability, and chaotic blood flow. The dysfunctional vasculature gives rise to continual plasma leakage and hypoxia in the tumor, resulting in constant on-sets of inflammation and angiogenesis. Tumors are thus likened to wounds that will not heal. The lack of functional mural cells, including pericytes and vascular smooth muscle cells, in tumor vascular structure contributes significantly to the abnormality of tumor vessels. Angiopoietin-1 (Ang 1) is aphysiological angiogenesis promoter during embryonic development. The function of Angl is essential to endothelial cell survival, vascular branching, and pericyte recruitment. However, an increasing amount of experimental data suggest that Angl-stimulated association of mural cells with endothelial cells lead to stabilization of newly formed blood vessels. This in turn may limit the otherwise continuous angiogenesis in the tumor, and consequently give riseto inhibition of tumor growth. We discuss the enigmatic role of Angl in tumor angiogenesis in this review.  相似文献   
993.
关于物种濒危等级标准之探讨--对IUCN物种濒危等级的思考   总被引:10,自引:3,他引:7  
为了保存地球上的生物多样性,我们需要根据物种的种群数量与分布、种群数量波动与分布区下降速率来评定濒危物种的濒危等级,并针对物种的濒危等级提出具体的保护措施。1994年11月,IUCN第40次理事会会议正式通过了经过修订的Mace-Lande物种濒危等级标准作为IUCN物种濒危等级标准。IUCN濒危物种红色名录虽然不是国际法和国家法律,但是对于政府间组织、非政府组织的保护决策以及各国的自然法律法规的制定有着深远的影响,在保护生物学理论研究中也发挥了一定作用。我们在研究制定中国水生野生生物濒危等级标准时发现,如果直接应用IUCN物种濒危等级标准评定水生野生生物濒危等级将存在一些问题。如:(1)如何区别对待那些本来就数量稀少、分布区狭窄的物种和那些由于人类活动而导致其种群数量与生境面积急剧下降的物种?(2)不同的动物类群能否应用同一濒危标准尺度?(3)如何区别对待物种边缘分布区和核心分布区的种群数量与密度的差异?(4)如何处理种群的局部灭绝、局部濒危?(5)一些濒危物种在野生环境中濒危,但是这些物种可以人工繁殖,如何处理可以人工繁殖的濒危物种?(6)如果没有种群与栖息地的精确历史资料和统计数据,怎样应用物种的濒危标准评估其濒危等级?在实践中,我们针对这些问题提出了解决方案。考虑与国际流行的IUCN物种濒危等级标准接轨,我们提出来一个由“无危”、“值得关注”、“受胁”、“濒危”和“灭绝”等5个级构成的濒危等级系统,其中“值得关注”、“受胁”、“濒危”又分为“一般”与“高度”两个亚等级。我们提出应区分“生态濒危物种”、“进化濒危物种”;对于不同生物类群,应区分物种的生活史对策,制定不同生活史物种的濒危标准。对于r-对策物种,引入“经济灭绝”这一等级,将这一等级对应于“受胁”等级,以解决缺少物种数量的统计数据和历史数据这一难题;区别对待特有物种,将其濒危等级提升一等;引进集合种群(metapopulation)概念,将集合种群的局域种群(local population)作为“个体”对待。  相似文献   
994.
In this study, we used a random approach to determine which amino acid pairs in human coagulation factor IX precursor are more sensitive to its 99 variants. The results show that the randomly unpredictable amino acid pairs are more sensitive to variants.  相似文献   
995.
This work describes in-depth NMR characterization of a unique low-barrier hydrogen bond (LBHB) between an active site residue from the enzyme and a bound inhibitor: the complex between secreted phospholipase A(2) (sPLA(2), from bee venom and bovine pancreas) and a transition-state analog inhibitor HK32. A downfield proton NMR resonance, at 17-18 ppm, was observed in the complex but not in the free enzyme. On the basis of site-specific mutagenesis and specific 15N-decoupling, this downfield resonance was assigned to the active site H48, which is part of the catalytic dyad D99-H48. These results led to a hypothesis that the downfield resonance represents the proton (H(epsilon 2) of H48) involved in the H-bonding between D99 and H48, in analogy with serine proteases. However, this was shown not to be the case by use of the bovine enzyme labeled with specific [15N(epsilon 2)]His. Instead, the downfield resonance arises from H(delta1) of H48, which forms a hydrogen bond with a non-bridging phosphonate oxygen of the inhibitor. Further studies showed that this proton displays a fractionation factor of 0.62(+/-0.06), and an exchange rate protection factor of >100 at 285 K and >40 at 298 K, which are characteristic of a LBHB. The pK(a) of the imidazole ring of H48 was shown to be shifted from 5.7 for the free enzyme to an apparent value of 9.0 in the presence of the inhibitor. These properties are very similar to those of the Asp em leader His LBHBs in serine proteases. Possible structural bases and functional consequences for the different locations of the LBHB between these two types of enzymes are discussed. The results also underscore the importance of using specific isotope labeling, rather than extrapolation of NMR results from other enzyme systems, to assign the downfield proton resonance to a specific hydrogen bond. Although our studies did not permit the strength of the LBHB to be accurately measured, the data do not provide support for an unusually strong hydrogen bond strength (i.e. >10 kcal/mol).  相似文献   
996.
The CD134-CD134 ligand (CD134L) costimulatory pathway has been shown to be critical for both T and B cell activation; however, its role in regulating the alloimmune response remains unexplored. Furthermore, its interactions with other costimulatory pathways and immunosuppressive agents are unclear. We investigated the effect of CD134-CD134L pathway blockade on allograft rejection in fully MHC-mismatched rat cardiac and skin transplantation models. CD134L blockade alone did not prolong graft survival compared with that of untreated recipients, and in combination with donor-specific transfusion, cyclosporine, or rapamycin, was less effective than B7 blockade in prolonging allograft survival. However, in combination with B7 blockade, long-term allograft survival was achieved in all recipients (>200 days). Moreover, this was synergistic in reducing the frequency of IFN-gamma-producing alloreactive lymphocytes and inhibiting the generation of activated/effector lymphocytes. Most impressively, this combination prevented rejection in a presensitized model using adoptive transfer of primed lymphocytes into athymic heart transplant recipients. In comparison to untreated recipients (mean survival time (MST): 5.3 +/- 0.5 days), anti-CD134L mAb alone modestly prolonged allograft survival (MST: 14 +/- 2.8 days) as did CTLA4Ig (MST: 21.5 +/- 1.7 days), but all grafts were rejected within 24 days. Importantly, combined blockade further and significantly prolonged allograft survival (MST: 75.3 +/- 12.7 days) and prevented the expansion and/or persistence of primed/effector alloreactive T cells. Our data suggest that CD134-CD134L is a critical pathway in alloimmune responses, especially recall/primed responses, and is synergistic with CD28-B7 in mediating T cell effector responses during allograft rejection. Understanding the mechanisms of collaboration between these different pathways is important for the development of novel strategies to promote long-term allograft survival.  相似文献   
997.
E1-deleted adenoviral recombinants most commonly based on the human serotype 5 (AdHu5) have been shown thus far to induce unsurpassed transgene product-specific CD8(+) T cell responses. A large percentage of the adult human population carries neutralizing Abs due to natural exposures to AdHu5 virus. To circumvent reduction of the efficacy of adenovirus (Ad) vector-based vaccines by neutralizing Abs to the vaccine carrier, we developed E1-deleted adenoviral vaccine carriers based on simian serotypes. One of these carriers, termed AdC68, expressing a codon-optimized truncated form of gag of HIV-1 was shown previously to induce a potent transgene product-specific CD8(+) T cell response in mice. We constructed a second chimpanzee adenovirus vaccine vector, termed AdC6, also expressing the truncated gag of HIV-1. This vector, which belongs to a different serotype than the AdC68 virus, induces high frequencies of gag-specific CD8(+) T cells in mice including those pre-exposed to AdHu5 virus. Generation of an additional E1-deleted adenoviral vector of chimpanzee origin allows for sequential booster immunizations with heterologous vaccine carriers. In this study, we show that such heterologous prime boost regimens based on E1-deleted adenoviral vectors of different serotypes expressing the same transgene product are highly efficient in increasing the transgene product-specific CD8(+) T cell response. They are equivalent to sequential vaccinations with an E1-deleted Ad vector followed by booster immunization with a poxvirus vector and they surpass regimens based on DNA vaccine prime followed by a recombinant adenoviral vector boost.  相似文献   
998.
The specificity of Ca2+ signals is conferred in part by limiting changes in cytosolic Ca2+ to subcellular domains. Mitochondria play a major role in regulating Ca2+ in neurons and may participate in its spatial localization. We examined the effects of changes in the distribution of mitochondria on NMDA-induced Ca2+ increases. Hippocampal cultures were treated with the microtubule-destabilizing agent vinblastine, which caused the mitochondria to aggregate and migrate towards one side of the neuron. This treatment did not appear to decrease the energy status of mitochondria, as indicated by a normal membrane potential and pH gradient across the inner membrane. Moreover, electron microscopy showed that vinblastine treatment altered the distribution but not the ultrastructure of mitochondria. NMDA (200 micro m, 1 min) evoked a greater increase in cytosolic Ca2+ in vinblastine-treated cells than in untreated cells. This increase did not result from impaired Ca2+ efflux, enhanced Ca2+ influx, opening of the mitochondrial permeability transition pore or altered function of endoplasmic reticulum Ca2+ stores. Ca2+ uptake into mitochondria was reduced by 53% in vinblastine-treated cells, as reported by mitochondrially targeted aequorin. Thus, the distribution of mitochondria maintained by microtubules is critical for buffering Ca2+ influx. A subset of mitochondria close to a Ca2+ source may preferentially regulate Ca2+ microdomains, set the threshold for Ca2+-induced toxicity and participate in local ATP production.  相似文献   
999.
Role of the ErbB-4 carboxyl terminus in gamma-secretase cleavage   总被引:1,自引:0,他引:1  
The ErbB-4 receptor tyrosine kinase has a PDZ domain recognition motif at its carboxyl terminus. The first step in ErbB-4 proteolytic processing is a metalloprotease-dependent cleavage of the receptor ectodomain, which is not influenced by deletion of this motif. Metalloprotease cleavage of ErbB-4 produces a membrane-associated 80-kDa fragment that is a substrate for subsequent gamma-secretase cleavage, which releases the cytoplasmic domain from the membrane and allows nuclear translocation of this fragment. Deletion of the PDZ domain recognition motif does abrogate the gamma-secretase cleavage of ErbB-4. The wild-type 80-kDa ErbB-4 fragment forms an association complex with presenilin, thought to be the catalytic moiety of gamma-secretase activity. However, this association is significantly impaired by loss of the PDZ domain recognition motif from ErbB-4. Deletion of this ErbB-4 motif prevents the nuclear localization of the ErbB-4 cytoplasmic domain. Data also show that the basal cleavage of wild-type ErbB-4 by this proteolytic system can produce a sufficient level of ErbB-4 processing to negatively influence cell growth and that loss of the PDZ domain recognition motif abrogates this response.  相似文献   
1000.
In a recent study, we reported that in bovine brain extract, glycogen synthase kinase-3beta and tau are parts of an approximately 400-500 kDa microtubule-associated tau phosphorylation complex (Sun, W., Qureshi, H. Y., Cafferty, P. W., Sobue, K., Agarwal-Mawal, A., Neufield, K. D., and Paudel, H. K. (2002) J. Biol. Chem. 277, 11933-11940). In this study, we find that when purified brain microtubules are subjected to Superose 12 gel filtration column chromatography, the dimeric scaffold protein 14-3-3 zeta co-elutes with the tau phosphorylation complex components tau and GSK3 beta. From gel filtration fractions containing the tau phosphorylation complex, 14-3-3 zeta, GSK3 beta, and tau co-immunoprecipitate with each other. From extracts of bovine brain, COS-7 cells, and HEK-293 cells transfected with GSK3 beta, 14-3-3 zeta co-precipitates with GSK3 beta, indicating that GSK3 beta binds to 14-3-3 zeta. From HEK-293 cells transfected with tau, GSK3 beta, and 14-3-3 zeta in different combinations, tau co-immunoprecipitates with GSK3 beta only in the presence of 14-3-3 zeta. In vitro, approximately 10-fold more tau binds to GSK3 beta in the presence of than in the absence of 14-3-3 zeta. In transfected HEK-293 cells, 14-3-3 zeta stimulates GSK3 beta-catalyzed tau phosphorylation in a dose-dependent manner. These data indicate that in brain, the 14-3-3 zeta dimer simultaneously binds and bridges tau and GSK3 beta and stimulates GSK3 beta-catalyzed tau phosphorylation.  相似文献   
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