全文获取类型
收费全文 | 15567篇 |
免费 | 1537篇 |
国内免费 | 2篇 |
专业分类
17106篇 |
出版年
2024年 | 16篇 |
2023年 | 97篇 |
2022年 | 217篇 |
2021年 | 375篇 |
2020年 | 233篇 |
2019年 | 272篇 |
2018年 | 324篇 |
2017年 | 294篇 |
2016年 | 506篇 |
2015年 | 954篇 |
2014年 | 923篇 |
2013年 | 1127篇 |
2012年 | 1468篇 |
2011年 | 1403篇 |
2010年 | 894篇 |
2009年 | 767篇 |
2008年 | 995篇 |
2007年 | 993篇 |
2006年 | 946篇 |
2005年 | 903篇 |
2004年 | 859篇 |
2003年 | 737篇 |
2002年 | 679篇 |
2001年 | 112篇 |
2000年 | 69篇 |
1999年 | 113篇 |
1998年 | 135篇 |
1997年 | 76篇 |
1996年 | 71篇 |
1995年 | 53篇 |
1994年 | 54篇 |
1993年 | 52篇 |
1992年 | 36篇 |
1991年 | 45篇 |
1990年 | 30篇 |
1989年 | 16篇 |
1988年 | 31篇 |
1987年 | 15篇 |
1986年 | 16篇 |
1985年 | 18篇 |
1984年 | 14篇 |
1983年 | 17篇 |
1982年 | 20篇 |
1981年 | 12篇 |
1980年 | 16篇 |
1979年 | 7篇 |
1978年 | 11篇 |
1977年 | 14篇 |
1976年 | 7篇 |
1974年 | 11篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
991.
992.
Hellman J Roberts JD Tehan MM Allaire JE Warren HS 《The Journal of biological chemistry》2002,277(16):14274-14280
Gram-negative bacterial sepsis commonly causes organ dysfunction and death in humans. Although circulating bacterial toxins trigger inflammation in sepsis, little is known about the composition of bacterial products released into the blood during sepsis or the contribution of various bacterial components to the pathogenesis of sepsis. We have shown that diverse Gram-negative bacteria release bacterial peptidoglycan-associated lipoprotein (PAL) into serum. The present studies explored release of PAL into the blood during sepsis and tested the hypothesis that PAL contributes to bacterial virulence and inflammation in Gram-negative sepsis. Released PAL was detected in the blood of 94% of mice following cecal ligation and puncture. Picomolar to nanomolar levels of PAL stimulated macrophages and splenocytes from lipopolysaccharide-hyporesponsive (C3H/HeJ) mice. Injection of PAL into C3H/HeJ mice stimulated production of serum cytokines and increased pulmonary and myocardial expression of inflammatory markers. PAL caused death in sensitized C3H/HeJ mice. Mutant Escherichia coli bacteria with reduced levels of PAL or truncated PAL were less virulent than wild-type bacteria, as indicated by higher survival rates and lower circulating levels of interleukin 6 and bacteria in a model of peritonitis in lipopolysaccharide-responsive mice. The studies suggest that PAL may be an important bacterial mediator of Gram-negative sepsis. 相似文献
993.
994.
Shanks RA Larocca MC Berryman M Edwards JC Urushidani T Navarre J Goldenring JR 《The Journal of biological chemistry》2002,277(43):40973-40980
AKAP350 can scaffold a number of protein kinases and phosphatases at the centrosome and the Golgi apparatus. We performed a yeast two-hybrid screen of a rabbit parietal cell library with a 3.2-kb segment of AKAP350 (nucleotides 3611-6813). This screen yielded a full-length clone of rabbit chloride intracellular channel 1 (CLIC1). CLIC1 belongs to a family of proteins, all of which contain a high degree of homology in their carboxyl termini. All CLIC family members were able to bind a 133-amino acid domain within AKAP350 through the last 120 amino acids in the conserved CLIC carboxyl termini. Antibodies developed against a bovine CLIC, p64, immunoprecipitated AKAP350 from HCA-7 colonic adenocarcinoma cell extracts. Antibodies against CLIC proteins recognized at least five CLIC species including a novel 46-kDa CLIC protein. We isolated the human homologue of bovine p64, CLIC5B, from HCA-7 cell cDNA. A splice variant of CLIC5, the predicted molecular mass of CLIC5B corresponds to the molecular mass of the 46-kDa CLIC immunoreactive protein in HCA-7 cells. Antibodies against CLIC5B colocalized with AKAP350 at the Golgi apparatus with minor staining of the centrosomes. AKAP350 and CLIC5B association with Golgi elements was lost following brefeldin A treatment. Furthermore, GFP-CLIC5B-(178-410) targeted to the Golgi apparatus in HCA-7 cells. The results suggest that AKAP350 associates with CLIC proteins and specifically that CLIC5B interacts with AKAP350 at the Golgi apparatus in HCA-7 cells. 相似文献
995.
IL-4 pretreatment selectively enhances cytokine and chemokine production in lipopolysaccharide-stimulated mouse peritoneal macrophages 总被引:1,自引:0,他引:1
Major J Fletcher JE Hamilton TA 《Journal of immunology (Baltimore, Md. : 1950)》2002,168(5):2456-2463
Although well recognized for its anti-inflammatory effect on gene expression in stimulated monocytes and macrophages, IL-4 is a pleiotropic cytokine that has also been shown to enhance TNF-alpha and IL-12 production in response to stimulation with LPS. In the present study we expand these prior studies in three areas. First, the potentiating effect of IL-4 pretreatment is both stimulus and gene selective. Pretreatment of mouse macrophages with IL-4 for a minimum of 6 h produces a 2- to 4-fold enhancement of LPS-induced expression of several cytokines and chemokines, including TNF-alpha, IL-1alpha, macrophage-inflammatory protein-2, and KC, but inhibits the production of IL-12p40. In addition, the production of TNF-alpha by macrophages stimulated with IFN-gamma and IL-2 is inhibited by IL-4 pretreatment, while responses to both LPS and dsRNA are enhanced. Second, the ability of IL-4 to potentiate LPS-stimulated cytokine production appears to require new IL-4-stimulated gene expression, because it is time dependent, requires the activation of STAT6, and is blocked by the reversible protein synthesis inhibitor cycloheximide during the IL-4 pretreatment period. Finally, IL-4-mediated potentiation of TNF-alpha production involves specific enhancement of mRNA translation. Although TNF-alpha protein is increased in IL-4-pretreated cells, the level of mRNA remains unchanged. Furthermore, LPS-stimulated TNF-alpha mRNA is selectively enriched in actively translating large polyribosomes in IL-4-pretreated cells compared with cells stimulated with LPS alone. 相似文献
996.
IFN-gamma-inducible protein 10 (CXCL10) contributes to airway hyperreactivity and airway inflammation in a mouse model of asthma 总被引:9,自引:0,他引:9
Medoff BD Sauty A Tager AM Maclean JA Smith RN Mathew A Dufour JH Luster AD 《Journal of immunology (Baltimore, Md. : 1950)》2002,168(10):5278-5286
Allergic asthma is an inflammatory disease of the airways characterized by eosinophilic inflammation and airway hyper-reactivity. Cytokines and chemokines specific for Th2-type inflammation predominate in asthma and in animal models of this disease. The role of Th1-type inflammatory mediators in asthma remains controversial. IFN-gamma-inducible protein 10 (IP-10; CXCL10) is an IFN-gamma-inducible chemokine that preferentially attracts activated Th1 lymphocytes. IP-10 is up-regulated in the airways of asthmatics, but its function in asthma is unclear. To investigate the role of IP-10 in allergic airway disease, we examined the expression of IP-10 in a murine model of asthma and the effects of overexpression and deletion of IP-10 in this model using IP-10-transgenic and IP-10-deficient mice. Our experiments demonstrate that IP-10 is up-regulated in the lung after allergen challenge. Mice that overexpress IP-10 in the lung exhibited significantly increased airway hyperreactivity, eosinophilia, IL-4 levels, and CD8(+) lymphocyte recruitment compared with wild-type controls. In addition, there was an increase in the percentage of IL-4-secreting T lymphocytes in the lungs of IP-10-transgenic mice. In contrast, mice deficient in IP-10 demonstrated the opposite results compared with wild-type controls, with a significant reduction in these measures of Th2-type allergic airway inflammation. Our results demonstrate that IP-10, a Th1-type chemokine, is up-regulated in allergic pulmonary inflammation and that this contributes to the airway hyperreactivity and Th2-type inflammation seen in this model of asthma. 相似文献
997.
Minor histocompatibility antigen-specific MHC-restricted CD8 T cell responses elicited by heat shock proteins 总被引:6,自引:0,他引:6
Robert J Gantress J Rau L Bell A Cohen N 《Journal of immunology (Baltimore, Md. : 1950)》2002,168(4):1697-1703
In mammals, the heat shock proteins (HSP) gp96 and hsp70 elicit potent specific MHC class I-restricted CD8(+) T cell (CTL) response to exogenous peptides they chaperone. We show in this study that in the adult frog Xenopus, a species whose common ancestors with mammals date back 300 million years, both hsp70 and gp96 generate an adaptive specific cellular immune response against chaperoned minor histocompatibility antigenic peptides that effects an accelerated rejection of minor histocompatibility-locus disparate skin grafts in vivo and an MHC-specific CD8(+) cytotoxic T cell response in vitro. In naturally class I-deficient but immunocompetent Xenopus larvae, gp96 also generates an antitumor immune response that is independent of chaperoned peptides (i.e., gp96 purified from normal tissue also generates a significant antitumor response); this suggests a prominent contribution of an innate type of response in the absence of MHC class I Ags. 相似文献
998.
The initiation and promotion of sporocyst propagation and subsequent production of cercariae by intramolluscan larval stages of digenic trematodes are thought to depend on mollusc-derived factors. The ability to investigate this using in vitro cultures of Schistosoma mansoni sporocysts has been impeded by the fact that plasma from the host, Biomphalaria glabrata, becomes toxic to the parasite in long-term cultures. The present study identifies hemoglobin as the plasma component responsible for this toxicity. The addition of the enzyme catalase to sporocyst cultures neutralized the toxic effects of both purified hemoglobin and whole plasma, suggesting that the generation of H2O2 as a consequence of hemoglobin oxidation is the mechanism of plasma toxicity. Furthermore, cultures incubated in unconditioned schistosome medium with plasma plus catalase yielded significantly higher numbers of daughter sporocysts than cultures with media or plasma alone, but not higher than cultures with catalase alone. These latter results suggest that the oxidative environment and the antioxidant capacity of the media are critical factors for in vitro propagation of S. mansoni sporocysts. 相似文献
999.
Construction and manipulation of an infectious clone of the bovine herpesvirus 1 genome maintained as a bacterial artificial chromosome 总被引:3,自引:0,他引:3 下载免费PDF全文
The complete genome of bovine herpesvirus 1 (BoHV-1) strain V155 has been cloned as a bacterial artificial chromosome (BAC). Following electroporation into Escherichia coli strain DH10B, the BoHV-1 BAC was stably propagated over multiple generations of its host. BAC DNA recovered from DH10B cells and transfected into bovine cells produced a cytopathic effect which was indistinguishable from that of the parent virus. Analysis of the replication kinetics of the viral progeny indicated that insertion of the BAC vector into the thymidine kinase gene did not affect viral replication. Specific manipulation of the BAC was demonstrated by deleting the gene encoding glycoprotein E by homologous recombination in DH10B cells facilitated by GET recombination. These studies illustrate that the propagation and manipulation of herpesviruses in bacterial systems will allow for rapid and accurate characterization of BoHV-1 genes. In turn, this will allow for the full utilization of BoHV-1 as a vaccine vector. 相似文献
1000.
General relationships between species diversity and stability in competitive systems 总被引:1,自引:0,他引:1
Investigating the effect of biodiversity on the stability of ecological communities is complicated by the numerous ways in which models of community interactions can be formulated. This has led to differences in conclusions and interpretations of how the number of species in a community affects its stability. Here, we derive a simple, general relationship between the coefficient of variation (CV) of combined species densities and the environmentally driven variability in species' per capita population growth rates. For a given level of environmentally driven variability in per capita population growth rates, increasing the number of species in a community decreases the CV of combined species densities, provided that species do not respond to environmental fluctuations in a perfectly correlated way. Thus, a community with more species of competitors will be more stable (have lower CV in combined species densities for a given level of environmental variability) than a species-poor community, provided that the species in both communities show equal variability in per capita population growth rates and provided that species within each community do not show strongly correlated responses to environmental fluctuations. This conclusion also applies to "noninteractive" models in which there is no competition between species. 相似文献