全文获取类型
收费全文 | 1323篇 |
免费 | 148篇 |
专业分类
1471篇 |
出版年
2023年 | 8篇 |
2022年 | 13篇 |
2021年 | 44篇 |
2020年 | 14篇 |
2019年 | 31篇 |
2018年 | 44篇 |
2017年 | 37篇 |
2016年 | 52篇 |
2015年 | 68篇 |
2014年 | 56篇 |
2013年 | 76篇 |
2012年 | 66篇 |
2011年 | 86篇 |
2010年 | 51篇 |
2009年 | 63篇 |
2008年 | 72篇 |
2007年 | 74篇 |
2006年 | 48篇 |
2005年 | 56篇 |
2004年 | 49篇 |
2003年 | 59篇 |
2002年 | 47篇 |
2001年 | 40篇 |
2000年 | 39篇 |
1999年 | 31篇 |
1998年 | 19篇 |
1997年 | 11篇 |
1996年 | 17篇 |
1995年 | 19篇 |
1994年 | 9篇 |
1993年 | 15篇 |
1992年 | 10篇 |
1991年 | 14篇 |
1990年 | 21篇 |
1989年 | 15篇 |
1988年 | 13篇 |
1987年 | 8篇 |
1986年 | 11篇 |
1985年 | 14篇 |
1984年 | 5篇 |
1983年 | 3篇 |
1982年 | 4篇 |
1979年 | 6篇 |
1978年 | 6篇 |
1977年 | 2篇 |
1976年 | 3篇 |
1974年 | 2篇 |
1972年 | 4篇 |
1971年 | 2篇 |
1967年 | 6篇 |
排序方式: 共有1471条查询结果,搜索用时 15 毫秒
191.
Carolina Lessa-Aquino Camila Borges Rodrigues Jozelyn Pablo Rie Sasaki Algis Jasinskas Li Liang Elsio A. Wunder Jr Guilherme S. Ribeiro Adam Vigil Ricardo Galler Douglas Molina Xiaowu Liang Mitermayer G. Reis Albert I. Ko Marco Alberto Medeiros Philip L. Felgner 《PLoS neglected tropical diseases》2013,7(10)
Background
Leptospirosis is a widespread zoonotic disease worldwide. The lack of an adequate laboratory test is a major barrier for diagnosis, especially during the early stages of illness, when antibiotic therapy is most effective. Therefore, there is a critical need for an efficient diagnostic test for this life threatening disease.Methodology
In order to identify new targets that could be used as diagnostic makers for leptopirosis, we constructed a protein microarray chip comprising 61% of Leptospira interrogans proteome and investigated the IgG response from 274 individuals, including 80 acute-phase, 80 convalescent-phase patients and 114 healthy control subjects from regions with endemic, high endemic, and no endemic transmission of leptospirosis. A nitrocellulose line blot assay was performed to validate the accuracy of the protein microarray results.Principal findings
We found 16 antigens that can discriminate between acute cases and healthy individuals from a region with high endemic transmission of leptospirosis, and 18 antigens that distinguish convalescent cases. Some of the antigens identified in this study, such as LipL32, the non-identical domains of the Lig proteins, GroEL, and Loa22 are already known to be recognized by sera from human patients, thus serving as proof-of-concept for the serodiagnostic antigen discovery approach. Several novel antigens were identified, including the hypothetical protein LIC10215 which showed good sensitivity and specificity rates for both acute- and convalescent-phase patients.Conclusions
Our study is the first large-scale evaluation of immunodominant antigens associated with naturally acquired leptospiral infection, and novel as well as known serodiagnostic leptospiral antigens that are recognized by antibodies in the sera of leptospirosis cases were identified. The novel antigens identified here may have potential use in both the development of new tests and the improvement of currently available assays for diagnosing this neglected tropical disease. Further research is needed to assess the utility of these antigens in more deployable diagnostic platforms. 相似文献192.
Cerón MC García-Malea MC Rivas J Acien FG Fernandez JM Del Río E Guerrero MG Molina E 《Applied microbiology and biotechnology》2007,74(5):1112-1119
The influence of culture conditions on the quality of Haematococcus pluvialis biomass is assessed. Continuously grown cells have been characterised with respect to their astaxanthin, fatty acid content,
and antioxidant activity and compared with those of non-growing haematocysts. Moderate limitation of nitrate availability
(1.7 mM) under continuous growth conditions favoured the production of reddish palmelloid cells whose extracts possessed antioxidant
activity equivalent to that of haematocyst extracts, despite the lower astaxanthin content (0.6%d.wt.), which is compensated
by a higher fatty acid level (7.6%d.wt.). Green cells produced under nitrate saturation conditions (>4.7 mM) exhibit only
40% antioxidant activity than palmelloid. In addition, the major fatty acid present in palmelloid cells was oleic acid (40%f.a.),
whereas, in both green cells and haematocysts, the main fatty acids were myristic, palmitic, and oleic acid (20–30%f.a. each).
Biomass extracts were fractionated and analysed. The antioxidant capacity was a function of both the carotenoid and the fatty
acid profiles, the antioxidant capacity of astaxanthin diesters fraction being 60% higher than astaxanthin monoesters fraction
and twice than free astaxanthin. In such a way, the evaluation of the quality of H. pluvialis biomass must take into account both variables. When considering the production of H. pluvialis biomass for human consumption, special attention should be paid to the one-step continuous system approach for the generation
of cells rich in both astaxanthin and fatty acids, as they have high antioxidant activity but without thick hard cell wall. 相似文献
193.
194.
Kalil-Gaspar P Marcuzzo S Rigon P Molina CG Achaval M 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2007,148(2):286-291
The aim of this study was to measure the nociceptive response (avoidance latency) of the land snail Megalobulimus abbreviatus (N=8 in each group) after topical capsaicin exposure (0.1% and 0.5% in 20% ethanol) and to compare it to a well-studied stressful (50 degrees C) thermal stimulus model. We also tested if ruthenium red, and capsazepine, respectively nonselective and selective TRPV1 receptor antagonists, could modify both capsaicin- and thermal-evoked responses. Finally, animals were pretreated with morphine, naloxone or morphine plus naloxone prior to capsaicin stimuli. Latencies were measured when the animal lifted its head-foot complex 1 cm from the substrate. Data were compared using ANOVA and LSD post hoc, and the Student T Test (p<0.05). Capsaicin elicited dose-dependent withdrawal behavior. The capsaicin vehicle (20% ethanol) also evoked a less intense but significant avoidance reaction. Capsazepine and ruthenium red attenuated both capsaicin and heat withdrawal responses, when compared to vehicles. Morphine increased, and naloxone, either alone or in combination with morphine, reduced capsaicin-evoked latencies when compared to morphine or saline. These results indicate that the TRPV1 receptor plays a role in the nociceptive circuits of M. abbreviatus. 相似文献
195.
Background
Fibroblast Growth Factors (FGFs) represent a large family of secreted proteins that are required for proper development and physiological processes. Mutations in mouse and zebrafish FGFs result in abnormal embryogenesis and lethality. A key to understanding the precise role for these factors is to determine their spatial and temporal activity during embryogenesis. 相似文献196.
A model for the recognition of protein kinases based on the entropy of 3D van der Waals interactions
Gonzalez-Díaz H Saiz-Urra L Molina R Santana L Uriarte E 《Journal of proteome research》2007,6(2):904-908
The study and prediction of kinase function (kinomics) is of major importance for proteome research due to the widespread distribution of kinases. However, the prediction of protein function based on the similarity between a functionally annotated 3D template and a query structure may fail, for instance, if a similar protein structure cannot be identified. Alternatively, function can be assigned using 3D-structural empirical parameters. In previous studies, we introduced parameters based on electrostatic entropy (Proteins 2004, 56, 715) and molecular vibration entropy (Bioinformatics 2003, 19, 2079) but ignored other important factors such as van der Waals (vdw) interactions. In the work described here, we define 3D-vdw entropies (degrees theta(k)) and use them for the first time to derive a classifier for protein kinases. The model classifies correctly 88.0% of proteins in training and more than 85.0% of proteins in validation studies. Principal components analysis of heterogeneous proteins demonstrated that degrees theta(k) codify information that is different to that described by other bulk or folding parameters. In additional validation experiments, the model recognized 129 out of 142 kinases (90.8%) and 592 out of 677 non-kinases (87.4%) not used above. This study provides a basis for further consideration of degrees theta(k) as parameters for the empirical search for structure-function relationships. 相似文献
197.
198.
M. Luisa Molina A. Marcela Giudici José A. Poveda Gregorio Fernández-Ballester Estefanía Montoya M. Lourdes Renart Asia M. Fernández José A. Encinar Gloria Riquelme Andrés Morales José M. González-Ros 《The Journal of biological chemistry》2015,290(42):25745-25755
There is increasing evidence to support the notion that membrane proteins, instead of being isolated components floating in a fluid lipid environment, can be assembled into supramolecular complexes that take part in a variety of cooperative cellular functions. The interplay between lipid-protein and protein-protein interactions is expected to be a determinant factor in the assembly and dynamics of such membrane complexes. Here we report on a role of anionic phospholipids in determining the extent of clustering of KcsA, a model potassium channel. Assembly/disassembly of channel clusters occurs, at least partly, as a consequence of competing lipid-protein and protein-protein interactions at nonannular lipid binding sites on the channel surface and brings about profound changes in the gating properties of the channel. Our results suggest that these latter effects of anionic lipids are mediated via the Trp67–Glu71–Asp80 inactivation triad within the channel structure and its bearing on the selectivity filter. 相似文献
199.
Nishikaku AS Molina RF Albe BP Cunha Cda S Scavone R Pizzo CR de Camargo ZP Burger E 《FEMS immunology and medical microbiology》2011,63(2):281-288
The important role of interferon-gamma (IFN-γ) in protective immunity in mycosis is well established, except for its participation in fungal granulomas. Herein, we employ immunohistochemical reactions to describe the in situ localization of IFN-γ in granulomas of susceptible (B10.A) and resistant (A/J) mice to infection with Paracoccidioides brasiliensis (Pb). After infection with the highly virulent Pb18, IFN-γ-positive lymphomononuclear cells were localized mainly at the periphery of granulomas in both mouse strains. The numbers of positive cells found in compact granulomas of A/J mice increased significantly from 15 to 120 days postinfection. At this time, significantly more positive cells were detected in the compact granulomas of resistant mice than in the loose, multifocal lesions of the susceptible ones. In infection with the slightly virulent Pb265, the same pattern of IFN-γ localization was found as in Pb18 infection, but there was decreased staining at 120 days due to the presence of only residual lesions in both mouse strains. The marked IFN-γ staining observed in the granulomas of resistant mice at the later stage of Pb infection confirms its importance in fungal dissemination control, and suggests a contribution to the development of paracoccidioidal granuloma. 相似文献
200.
Molecular cloning of IGF-1 and IGF-1 receptor and their expression pattern in the Chilean flounder (Paralichthys adspersus) 总被引:1,自引:0,他引:1