全文获取类型
收费全文 | 996篇 |
免费 | 69篇 |
专业分类
1065篇 |
出版年
2023年 | 10篇 |
2022年 | 10篇 |
2021年 | 29篇 |
2020年 | 16篇 |
2019年 | 12篇 |
2018年 | 28篇 |
2017年 | 19篇 |
2016年 | 17篇 |
2015年 | 47篇 |
2014年 | 43篇 |
2013年 | 67篇 |
2012年 | 71篇 |
2011年 | 65篇 |
2010年 | 52篇 |
2009年 | 39篇 |
2008年 | 49篇 |
2007年 | 66篇 |
2006年 | 51篇 |
2005年 | 47篇 |
2004年 | 48篇 |
2003年 | 30篇 |
2002年 | 33篇 |
2001年 | 17篇 |
2000年 | 20篇 |
1999年 | 12篇 |
1998年 | 5篇 |
1996年 | 8篇 |
1995年 | 4篇 |
1994年 | 5篇 |
1993年 | 9篇 |
1992年 | 7篇 |
1991年 | 5篇 |
1990年 | 7篇 |
1989年 | 7篇 |
1988年 | 8篇 |
1987年 | 9篇 |
1986年 | 5篇 |
1985年 | 4篇 |
1984年 | 7篇 |
1983年 | 5篇 |
1982年 | 8篇 |
1981年 | 5篇 |
1980年 | 9篇 |
1979年 | 10篇 |
1977年 | 8篇 |
1976年 | 5篇 |
1974年 | 3篇 |
1973年 | 6篇 |
1972年 | 4篇 |
1968年 | 2篇 |
排序方式: 共有1065条查询结果,搜索用时 9 毫秒
951.
Pillai AD Rathod PD Franklin PX Padh H Vasu KK Sudarsanam V 《Biochemical and biophysical research communications》2004,317(4):1067-1074
A series of novel tetra substituted thiophenes were synthesized, characterized, and evaluated for their anti-inflammatory activity in carrageenin induced rat paw edema model-an acute in vivo model. Compounds V1, V3, V11, V12, V17, and V18 showed good anti-inflammatory activity, indicating the importance of oxime moiety in modulating the activity. The structure-activity relationship studies explore "the aliphatic oxime esters" attached via a ketone bridge to fifth position of the thiophene, and indicate that this feature may enhance the anti-inflammatory activity as compared to aromatic oximes. Since free radicals are implicated in various inflammatory disorders, the free radical scavenging activity of some of the synthesized candidates was assessed using 1,1-diphenyl-2-picryl hydrazyl assay. The oxime containing analogs exhibited weak to moderate activity as free radical scavengers in DPPH assay. A plausible reasoning for its free radical scavenging ability is discussed. All the compounds were also screened in nitro blue tetrazolium model, to assess them as superoxide anion radical scavengers. A direct correlation between anti-inflammatory activity and free radical scavenging activity was not seen. The results disclose a new class of anti-inflammatory agents designed and synthesized for the first time wherein the utility of aliphatic oxime esters in modulating the anti-inflammatory activity profile is apparent. This will give us potential anti-inflammatory leads. 相似文献
952.
953.
954.
Selvamurugan N Kwok S Alliston T Reiss M Partridge NC 《The Journal of biological chemistry》2004,279(18):19327-19334
955.
Short duration of elevated vIRF-1 expression during lytic replication of human herpesvirus 8 limits its ability to block antiviral responses induced by alpha interferon in BCBL-1 cells 总被引:3,自引:0,他引:3 下载免费PDF全文
Pozharskaya VP Weakland LL Zimring JC Krug LT Unger ER Neisch A Joshi H Inoue N Offermann MK 《Journal of virology》2004,78(12):6621-6635
Human herpesvirus 8 (HHV-8) encodes multiple proteins that disrupt the host antiviral response, including viral interferon (IFN) regulatory factor 1 (vIRF-1). The product of the vIRF-1 gene blocks responses to IFN when overexpressed by transfection, but the functional consequence of vIRF-1 that is expressed during infection with HHV-8 is not known. These studies demonstrate that BCBL-1 cells that were latently infected with HHV-8 expressed low levels of vIRF-1 that were associated with PML bodies, whereas much higher levels of vIRF-1 were transiently expressed during the lytic phase of HHV-8 replication. The low levels of vIRF-1 that were associated with PML bodies were insufficient to block alpha IFN (IFN-alpha)-induced alterations in gene expression, whereas cells that expressed high levels of vIRF-1 were resistant to some changes induced by IFN-alpha, including the expression of the double-stranded-RNA-activated protein kinase. High levels of vIRF-1 were expressed for only a short period during the lytic cascade, so many cells with HHV-8 in the lytic phase responded to IFN-alpha with increased expression of antiviral genes and enhanced apoptosis. Furthermore, the production of infectious virus was severely compromised when IFN-alpha was present early during the lytic cascade. These studies indicate that the transient expression of high levels of vIRF-1 is inadequate to subvert many of the antiviral effects of IFN-alpha so that IFN-alpha can effectively induce apoptosis and block production of infectious virus when present early in the lytic cascade of HHV-8. 相似文献
956.
957.
Mahesh Kumar MJ Nagarajan P Venkatesan R Sakthivelan SM Majumdar SS 《Journal of medical primatology》2004,33(4):214-218
A tumor mass was identified below the shoulder region of a 5-year-old male rhesus monkey (Macaca mulatta). The mass was excised and diagnosed as sebaceous gland adenoma based on the microscopic findings. Morphologically it appeared as an elevated, dome-shaped, circumscribed mass of 3.6 x 2.8 x 3.2 cm in dimension with tan speckled color. Histologically, the tumor was composed of mature, sebaceous cells (sebocytes), basal cells arranged in a mass of irregular shapes and sizes, with a characteristic appearance of poly or multilobular structure. Sebocytes were well differentiated with foamy cytoplasm in the center of the lobules and poorly or undifferentiated densely staining basal cells in the periphery of the lobules. Cellular changes in the adjacent lymph node included hyperplasia of plasma cells, macrophages and lymphoid elements with typical mitosis. 相似文献
958.
959.
Cloning and characterization of a gene cluster for cyclododecanone oxidation in Rhodococcus ruber SC1 下载免费PDF全文
Biological oxidation of cyclic ketones normally results in formation of the corresponding dicarboxylic acids, which are further metabolized in the cell. Rhodococcus ruber strain SC1 was isolated from an industrial wastewater bioreactor that was able to utilize cyclododecanone as the sole carbon source. A reverse genetic approach was used to isolate a 10-kb gene cluster containing all genes required for oxidative conversion of cyclododecanone to 1,12-dodecanedioic acid (DDDA). The genes required for cyclododecanone oxidation were only marginally similar to the analogous genes for cyclohexanone oxidation. The biochemical function of the enzymes encoded on the 10-kb gene cluster, the flavin monooxygenase, the lactone hydrolase, the alcohol dehydrogenase, and the aldehyde dehydrogenase, was determined in Escherichia coli based on the ability to convert cyclododecanone. Recombinant E. coli strains grown in the presence of cyclododecanone accumulated lauryl lactone, 12-hydroxylauric acid, and/or DDDA depending on the genes cloned. The cyclododecanone monooxygenase is a type 1 Baeyer-Villiger flavin monooxygenase (FAD as cofactor) and exhibited substrate specificity towards long-chain cyclic ketones (C11 to C15), which is different from the specificity of cyclohexanone monooxygenase favoring short-chain cyclic compounds (C5 to C7). 相似文献
960.
The primary objective of this study was to evaluate the effect of drug loading on the release of leuprolide acetate from an injectable polymeric implant, formed in situ, and efficacy of the released drug in suppressing serum testosterone levels in dogs for at least 90 days. An additional objective was to compare the optimum implant formulation with a commercial microsphere product. Evaluated implant formulations contained 45% w/w 75/25 poly (DL-lactide-co-glycolide) polymer having an intrinsic viscosity of 0.20 dL/g, dissolved in N-methyl-2-pyrrolidone. Irradiated polymer solution was mixed with leuprolide at different drug loads (3%, 4.5%, and 6% w/w) prior to subcutaneous administration to dogs. Dog serum was analyzed for testosterone (RIA) and leuprolide (LC/MS/MS) levels and comparisons within the three implant formulation groups were made. Varying the drug load did not significantly affect the release of leuprolide or efficacy of the implant formulation. Thus, the 6% w/w formulation with the smaller injection volume was selected for comparison with the commercial LUPRON Depot product, which was administered intramuscularly at a similar dosage. These comparisons of serum testosterone and leuprolide levels showed no significant difference in the pharmacologic efficacy even though drug levels were different at a number of points. This was mainly due to associated high standard deviations. Based on these studies, the 6% w/w leuprolide implant formulation was considered to be a suitable candidate for further development. Additional benefits of this system include its simple manufacturing and lower costs. 相似文献