全文获取类型
收费全文 | 4063篇 |
免费 | 268篇 |
国内免费 | 3篇 |
出版年
2023年 | 24篇 |
2022年 | 32篇 |
2021年 | 132篇 |
2020年 | 98篇 |
2019年 | 111篇 |
2018年 | 134篇 |
2017年 | 127篇 |
2016年 | 181篇 |
2015年 | 238篇 |
2014年 | 304篇 |
2013年 | 310篇 |
2012年 | 377篇 |
2011年 | 309篇 |
2010年 | 200篇 |
2009年 | 175篇 |
2008年 | 210篇 |
2007年 | 189篇 |
2006年 | 193篇 |
2005年 | 165篇 |
2004年 | 148篇 |
2003年 | 130篇 |
2002年 | 91篇 |
2001年 | 59篇 |
2000年 | 48篇 |
1999年 | 39篇 |
1998年 | 25篇 |
1997年 | 17篇 |
1996年 | 20篇 |
1995年 | 12篇 |
1994年 | 11篇 |
1993年 | 12篇 |
1992年 | 19篇 |
1991年 | 17篇 |
1990年 | 13篇 |
1989年 | 15篇 |
1988年 | 9篇 |
1987年 | 9篇 |
1986年 | 7篇 |
1985年 | 12篇 |
1984年 | 9篇 |
1983年 | 7篇 |
1982年 | 7篇 |
1980年 | 9篇 |
1979年 | 13篇 |
1978年 | 11篇 |
1977年 | 10篇 |
1975年 | 6篇 |
1974年 | 4篇 |
1973年 | 5篇 |
1972年 | 5篇 |
排序方式: 共有4334条查询结果,搜索用时 635 毫秒
1.
Sacramento Doralice Rodrigues Coelho Rosalie Reed Rodrigues Wigg Márcia Dutra Toledo Luna Linhares Luiz Fernando de Matos dos Santos Marta Gonçalves Azevedo Soares Semêdo Luzia Teixeira de Ribeiro da Silva Antonio Jorge 《World journal of microbiology & biotechnology》2004,20(3):225-229
A promising producer of bioactive compounds isolated from a Brazilian tropical soil was tested for its range of antimicrobial
activities. Strain 606, classified as Streptomyces sp., could not be identified up to species level, suggesting a possible new taxon. The supernatant and 10 extracts and fractions,
obtained by extraction and chromatographic techniques, presented antimicrobial activity using antibiograms. The methanolic
fraction was highly active against pathogenic bacteria, phytopathogenic fungi and the human pathogenic yeast Candida albicans. It also possessed high antiviral activity inhibiting the propagation of an acyclovir-resistant herpes simplex virus type
1 strain on HEp-2 cells at non-cytotoxic concentration. The strong cytotoxic effect suggests an antitumour action.
This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献
2.
Transthyretin (TTR) protects against A-Beta toxicity by binding the peptide thus inhibiting its aggregation. Previous work showed different TTR mutations interact differently with A-Beta, with increasing affinities correlating with decreasing amyloidogenecity of the TTR mutant; this did not impact on the levels of inhibition of A-Beta aggregation, as assessed by transmission electron microscopy. Our work aimed at probing differences in binding to A-Beta by WT, T119M and L55P TTR using quantitative assays, and at identifying factors affecting this interaction. We addressed the impact of such factors in TTR ability to degrade A-Beta. Using a dot blot approach with the anti-oligomeric antibody A11, we showed that A-Beta formed oligomers transiently, indicating aggregation and fibril formation, whereas in the presence of WT and T119M TTR the oligomers persisted longer, indicative that these variants avoided further aggregation into fibrils. In contrast, L55PTTR was not able to inhibit oligomerization or to prevent evolution to aggregates and fibrils. Furthermore, apoptosis assessment showed WT and T119M TTR were able to protect against A-Beta toxicity. Because the amyloidogenic potential of TTR is inversely correlated with its stability, the use of drugs able to stabilize TTR tetrameric fold could result in increased TTR/A-Beta binding. Here we showed that iododiflunisal, 3-dinitrophenol, resveratrol, [2-(3,5-dichlorophenyl)amino] (DCPA) and [4-(3,5-difluorophenyl)] (DFPB) were able to increase TTR binding to A-Beta; however only DCPA and DFPB improved TTR proteolytic activity. Thyroxine, a TTR ligand, did not influence TTR/A-Beta interaction and A-Beta degradation by TTR, whereas RBP, another TTR ligand, not only obstructed the interaction but also inhibited TTR proteolytic activity. Our results showed differences between WT and T119M TTR, and L55PTTR mutant regarding their interaction with A-Beta and prompt the stability of TTR as a key factor in this interaction, which may be relevant in AD pathogenesis and for the design of therapeutic TTR-based therapies. 相似文献
3.
Antigen presenting cells (APCs) in skin can promote either antigen-specific effector functions or antigen tolerance, and thus determine clearance or persistence of cutaneous viral infections. Human papillomavirus (HPV) infections can persist in squamous epithelium in immunocompetent individuals, and some persisting HPV infections, particularly with HPV16, promote malignant epithelial transformation. Here, we investigate whether local expression of the HPV16 protein most associated with malignant transformation, HPV16-E7, affects the phenotype and function of APC subsets in the skin. We demonstrate an expanded population of Langerhans cells in HPV16-E7 transgenic skin with distinct cell surface markers which express immune-modulatory enzymes and cytokines not expressed by cells from non transgenic skin. Furthermore, HPV16-E7 transgene expression in keratinocytes attracts new APC subsets to the epidermis. In vivo migration and transport of antigen to the draining lymph node by these APCs is markedly enhanced in HPV16-E7 expressing skin, whereas antigen-processing, as measured by proteolytic cleavage of DQ-OVA and activation of T cells in vivo by APCs, is significantly impaired. These data suggest that local expression of HPV16-E7 in keratinocytes can contribute to persisting infection with this oncogenic virus, by altering the phenotype and function of local APCs. 相似文献
4.
Vasant Chellappa Kendra N. Taylor Kathryn Pedrick Carlos Donado Ilka Arun Netravali Khaleda Haider Annaiah Cariappa Natasha F. Dalomba Shiv Pillai 《PloS one》2013,8(1)
Catalytically defective rare variants of Sialic acid Acetyl Esterase (SIAE) have previously been linked to autoimmunity. Studies presented here confirm that the M89V SIAE protein and all other products of common variant alleles of SIAE are catalytically normal. Although overexpressing transfected non-lymphoid cells secrete small amounts of SIAE that can associate with the cell surface, normal human lymphocytes do not exhibit cell surface SIAE, supporting genetic evidence in mice that indicates that this protein functions in a lymphocyte intrinsic manner. Analyses of the plasma proteome also indicate that SIAE is not secreted in vivo. A re-analysis exclusively of catalytically defective rare variant alleles of SIAE in subjects in which this gene was completely sequenced confirmed an association of SIAE with autoimmunity. A subset of catalytically defective rare variant SIAE alleles has previously been typed in a large genotyping study comparing a diverse group of disease subjects and controls; our re-analysis of this data shows that catalytically defective alleles are enriched in disease subjects. These data suggest that SIAE may be associated with autoimmunity and that further study of catalytically defective rare variant SIAE alleles in terms of autoimmune disease susceptibility is strongly warranted. 相似文献
5.
Emmanuelle Fontoura José Darival Ferreira Jamile Bubadué Ana Maria Ribeiro Leonardo Kerber 《Journal of morphology》2020,281(10):1223-1240
A diverse fossil record of Cervidae (Mammalia) has been documented in the South American Pleistocene, when these animals arrived during the Great American Biotic Interchange. Using computed tomography-scanning techniques, it is possible to access the endocranial morphology of extinct species. Here, we studied the brain endocast of the extinct late Pleistocene cervid Antifer ensenadensis from southern Brazil, one of the largest forms that lived on this continent, using comparative morphology, geometric morphometrics, and encephalization quotients. The analyzed endocasts demonstrate that A. ensenadensis had a gyrencephalic brain, showing a prominent longitudinal sinus (=sagittal superior sinus), which is also observed in the large South American cervid Blastocerus dichotomus. The encephalization quotient is within the variation of extant cervids, suggesting maintenance of the pattern of encephalization from at least the late Pleistocene. Geometric morphometric analysis suggested a clear and linear allometric trend between brain endocast size and shape, and highlights A. ensenadensis as an extreme form within the analyzed cervids regarding brain morphology. 相似文献
6.
7.
Felipe Silva de Andrade Thiago Ribeiro de Carvalho Lucas Borges Martins Ariovaldo Antonio Giaretta 《Studies on Neotropical Fauna and Environment》2017,52(2):157-167
In this study, we re-describe the advertisement and territorial calls of Boana pardalis, carry out an acoustic comparison between the studied species and the other congeners of the B. faber group, and report for the first time the tympanic amplexus for the studied species. The advertisement call of B. pardalis can be used to supplement its diagnosis in the B. faber group based on temporal call traits, e.g. emission rate and emission pattern, as well as the call envelope. 相似文献
8.
S Ribeiro C S Alviano F C Silva-Filho E F da Silva J Angluster W de Souza 《Microbios》1989,57(231):121-129
The surface anionic groups of Entamoeba invadens were analysed by cell electrophoresis, by ultrastructural cytochemistry, and by identification of sialic acids using paper and gas-liquid chromatography. Binding of colloidal iron hydroxide (CIH) and of cationized ferritin (CF) particles at pH 1.8 and 7.2, respectively, was observed on the cell surface. E. invadens has a highly negative surface charge (-0.96 microns s-1 V-1 cm). Treatment of the cells with trypsin and neuraminidase significantly reduced the electrophoretic mobility by 24% and 40%, respectively. Treatment of the amoebae with neuraminidase also markedly decreased the binding of CIH to the cell surface. This finding suggests that sialic acid residues are the major anionogenic groups exposed on the surface of E. invadens. Paper and gas-liquid chromatography showed that N-acetylneuraminic acid was the only derivative characterized in E. invadens. 相似文献
9.
E Mansini E G Oestreicher L P Ribeiro 《Archives internationales de physiologie et de biochimie》1989,97(6):447-453
Purified mitochondrial malate dehydrogenase isoenzyme (m-MDH) of Toxocara canis muscle presented maximum activity at 48 degrees C. A clear change in slope of the Arrhenius plot was observed. The energy of activation calculated for the catalytic process showed values of 3.2 kcal/mol and 10.5 kcal/mol. Thermal inactivation of m-MDH showed that it is more thermolabile than the s-isoenzyme. The inactivation of the enzyme by heat could be reduced at least in part by the addition of 0.1 mM NADH. The heat denaturation showed to be a first-order process. The rate constant (k) was calculated as being of the order of 5.28 X 10(-4) s-1 at 40 degrees C. The activation energy for the heat inactivation process was 16.45 kcal/mol between 30 degrees C and 40 degrees C and 13.79 kcal/mol between 40 degrees C and 48 degrees C. 相似文献
10.
The relationship between actual and perceived profitability was investigated by quantifying choice behavior of foraging honey bees (Apis mellifera).Rate of net energy gain was used as a measure of profitability. Individual bees repeatedly chose between a yellow and a blue tubular artificial flower which had different associated profitabilities. Handling costs were manipulated by using flowers of different depth;energy gains were manipulated by using different volumes of a 20% (w/w) sucrose solution. Bees' discrimination between the two flowers increased as the absolute difference in profitabilities increased and discrimination decreased as profitabilities of both flowers increased. Therefore, discrimination depended on the relative difference in profitability between flowers, and therefore, perception was a nonlinear function of actual rates of net energy gain. The results also suggested that motivation to choose between flowers depended on the level of profitability. We suggest that nonlinear perceptual scales and motivation should be incorporated into models of food choice as constraints and should be considered in the design of experiments used to test predictions of models and in the interpretation of experimental results. 相似文献