全文获取类型
收费全文 | 246篇 |
免费 | 13篇 |
出版年
2024年 | 1篇 |
2022年 | 1篇 |
2021年 | 5篇 |
2020年 | 1篇 |
2019年 | 2篇 |
2018年 | 3篇 |
2017年 | 1篇 |
2016年 | 10篇 |
2015年 | 12篇 |
2014年 | 16篇 |
2013年 | 23篇 |
2012年 | 25篇 |
2011年 | 20篇 |
2010年 | 18篇 |
2009年 | 10篇 |
2008年 | 13篇 |
2007年 | 9篇 |
2006年 | 9篇 |
2005年 | 22篇 |
2004年 | 6篇 |
2003年 | 9篇 |
2002年 | 7篇 |
2001年 | 4篇 |
2000年 | 1篇 |
1999年 | 5篇 |
1998年 | 6篇 |
1997年 | 3篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1993年 | 5篇 |
1992年 | 3篇 |
1991年 | 2篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1975年 | 1篇 |
排序方式: 共有259条查询结果,搜索用时 203 毫秒
81.
María G. Guevara Claudia R. Oliva Milagros Machinandiarena Gustavo R. Daleo 《Physiologia plantarum》1999,106(2):164-169
A protease was isolated from potato ( Solanum tuberosum L. cv. Huinkul) tuber disks after 24 h of aeration when proteolysis is markedly increased. Purification was performed by ammonium sulfate precipitation, ion exchange chromatography, and affinity chromatography. A size of 40 kDa was estimated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and gel filtration, it is monomeric and its properties are consistent with those of aspartic proteinases (EC 3.4.23): it had a pH optimum between 4 and 5 and it was inhibited by pepstatin. Partial homology with other plant aspartic proteinases was observed in two sequenced tryptic fragments. It binds to Sepharose-concanavalin A and can be eluted with α -methyl mannoside, indicating that it is possibly glycosylated. Unlike other aspartic proteinases from Solanaceae that degrade pathogenesis-related proteins, it is unable to cleave a basic chitinase from potato. Moreover, this aspartic protease is strongly inhibited by the basic chitinase; the 50% inhibition is obtained when the molar ratio approaches 1, the same as with pepstatin. The interaction between this aspartic protease and a new type of endogenous inhibitor may be an interesting starting point to study the regulation of these aspartic proteases during stress. 相似文献
82.
83.
Estradiol is a potent hypophagic agent that reduces food intake and body weight without a concomitant fall in plasma leptin levels. We investigated whether the hypophagic effect of estradiol is mediated by stimulating POMC and/or inhibiting NPY neuronal pathways in the hypothalamus, which respectively inhibit and stimulate feeding. We examined hypothalamic gene expression of Ob-Rb, NPY, POMC, MC4-R, and AgRP in intact Wistar rats treated with estradiol for 48 hours. Food intake and body weight were reduced in estradiol-treated rats but fat mass was unchanged; plasma leptin and insulin levels were not significantly different from untreated, freely fed controls. In untreated rats that were pair-fed to match the estradiol-treated group, body weight was also reduced without changes in fat mass, although leptin and insulin levels decreased significantly. Ob-Rb expression was increased in both hypophagic groups despite serum leptin were only decreased in pair-fed animals, suggesting an estradiol-stimulating effect on Ob-Rb expression. No significant differences were found in POMC, AgRP, or MC4-R expression among any of the experimental groups. A significant but small decrease in NPY expression was also found in both hypophagic groups; this was explained by the combined effect of both surgery and reduced food intake. These results indicate that estradiol mediated hypophagia in intact rats could be brought about by an enhanced hypothalamic leptin sensitivity but is unlikely to be driven by changes in NPY or melanocortin system. 相似文献
84.
Amrán D Sancho P Fernández C Esteban D Ramos AM de Blas E Gómez M Palacios MA Aller P 《Biochimica et biophysica acta》2005,1743(3):269-279
It has been reported that inhibition of extracellular signal-regulated protein kinases (ERKs) attenuates the toxicity cisplatin (cis-platinum (II)-diammine dichloride) in some cell types. This response was here investigated using human myeloid leukemia cells. Cisplatin stimulated ERK1/2 phosphorylation and caused apoptosis in U-937 promonocytic cells, an effect which was attenuated by the MEK/ERK inhibitors PD98059 and U0126. While ERK1/2 activation was a general phenomenon, irrespective of the used cell type or antitumour drug, the MEK/ERK inhibitors only reduced cisplatin toxicity in human myeloid cells (THP-1, HL-60 and NB-4), but not in RAW 264.7 mouse macrophages and NRK-52E rat renal tubular cells; and failed to reduce the toxicity etoposide, camptothecin, melphalan and arsenic trioxide, in U-937 cells. U0126 attenuated cisplatin-DNA binding and intracellular peroxide accumulation, which are important regulators of cisplatin toxicity. Although cisplatin decreased the intracellular glutathione (GSH) content, which was restored by U0126, treatments with GSH-ethyl ester and dl-buthionine-(S,R)-sulfoximine revealed that GSH does not regulate cisplatin toxicity in the present experimental conditions. In spite of it, PD98059 and U0126 reduced the intracellular accumulation of cisplatin. These results suggest that GSH-independent modulation of drug transport is a major mechanism explaining the anti-apoptotic action of MEK/ERK inhibitors in cisplatin-treated myeloid cells. 相似文献
85.
86.
87.
Effects of chronic quercetin treatment on hepatic oxidative status of spontaneously hypertensive rats 总被引:2,自引:0,他引:2
Duarte J Galisteo M Ocete MA Pérez-Vizcaino F Zarzuelo A Tamargo J 《Molecular and cellular biochemistry》2001,221(1-2):155-160
The effects of chronic administration of an oral daily dose of quercetin (10 mg Kg–1), the most abundant dietary flavonoid, were investigated on hepatic oxidative status in spontaneously hypertensive rats and normotensive Wistar Kyoto rats. Decreased liver glutathione peroxidase activity, increased liver total glutathione levels and increased both hepatic and plasmatic malondialdehyde concentrations were observed in spontaneously hypertensive rats when compared to Wistar Kyoto rats. In spontaneously hypertensive rats, treatment with quercetin for 5 weeks reduced blood pressure, increased glutathione peroxidase activity and reduced both plasma and hepatic malondialdehyde levels. However, none of these effects were observed in Wistar Kyoto rats. In conclusion, quercetin shows both antihypertensive and antioxidant properties in this model of genetic hypertension. 相似文献
88.
Lazo PA Nadal M Ferrer M Area E Hernández-Torres J Nabokina SM Mollinedo F Estivill X 《Human genetics》2001,108(3):211-215
Synaptosome-associated protein-23 (SNAP23) is a component of the cellular mechanism required for specific membrane fusion and targetting of intracellular vesicles. We have cloned the full-length human cDNA and the SNAP23 gene. The SNAP23 gene has eight exons, with the initiation codon located in exon 2, and maps to the human chromosome 15q21-22 region. The human SNAP23 gene can generate two types of message, the full-length message (SNAP23A) and a shorter message (SNAP23B). The latter is the result of alternative splicing where exon 5 is joined to exon 7 and the skipping of exon 6; it thus lacks a region that is required for non-specific binding to plasma membranes. The two isoforms, expressed as fusion proteins with glutathione-S-transferase, interact in vitro with human syntaxin 6, thus retaining the specific protein interaction required for membrane fusion. Alterations in the SNAP23 gene might be involved in neurological and other diseases with defects in vesicle-membrane fusion processes that map to 15q15-21. 相似文献
89.
Cristina Bocanegra Sara Gallego Jacobo Mendioroz Milagros Moreno Elena Sulleiro Fernando Salvador Nicolau Sikaleta Arlette Nindia Daniel Tchipita Morais Joromba Sebastiao Kavaya Adrián Sánchez Montalvá Teresa López Israel Molina 《PLoS neglected tropical diseases》2015,9(10)
Introduction
Schistosomiasis remains a public health major problem and little is known in many areas, mainly in Sub-Saharan AfricaObjectives
To assess the burden and risk factors of schistosomiasis and intestinal parasitic helminthes in the children of Cubal, Angola, and to compare different diagnostic approaches for urinary schistosomiasis under field conditions.Methods
A cross-sectional study was conducted. Urine and faeces samples of school children were microscopically studied. A random sample of children was obtained from an alphabetically arranged list of children, taking one of two children. Urine dipstick, colorimetric test and macrohaematuria were considered as indirect diagnostic methods and compared to direct urine examination. Possible risk factors for the infection were sex, age, distance to the river and previous treatment with praziquantel; the assessment was performed using Chi-square test.Results
A total of 785 (61.18%) children showed S. haematobium eggs in urine; children living within 500 meters from the river had a higher odds for infection: Odds ratio 1.97 (1.45–2.7 CI 95%); urine dipstick showed sensitivity of 96% and specificity of 61.3%, with a positive predictive value; colorimetric test showed sensitivity of 52.5%, specificity of 74.6% and a positive predictive value of 77%. Proteinuria was present in 653 (51.1%) children, being more frequent in children with S. haematobium in urine (75.2%); 32 of 191 stool samples (16%) showed the presence of other intestinal parasites and 8 (4%) for S. haematobium.Conclusions
Prevalence of urinary schistosomiasis in our study area is much higher than the national average, considering it as a high-risk community. Proximity to a source of water was a risk factor for the infection. Indirect tests, as urine dipstick and colorimetric test, were useful tools for diagnosis, due to ease of use and low cost. Proteinuria was a common finding, probably showing an early structural damage due to schistosomiasis in this group of children. 相似文献90.
Hugo Valdivia-Olarte David Requena Manuel Ramirez Luis E Saravia Ray Izquierdo Francesca Falconi-Agapito Milagros Zavaleta Iván Best Manolo Fernández-Díaz Mirko Zimic 《Bioinformation》2015,11(10):460-465
Fowl adenoviruses (FAdVs) are the ethiologic agents of multiple pathologies in chicken. There are five different species of FAdVs
grouped as FAdV-A, FAdV-B, FAdV-C, FAdV-D, and FAdV-E. It is of interest to develop immunodiagnostics and vaccine
candidate for Peruvian FAdV-C in chicken infection using MHC restricted short peptide candidates.
We sequenced the complete genome of one FAdV strain isolated from a chicken of a local farm. A total of 44 protein coding genes
were identified in each genome. We sequenced twelve Cobb chicken MHC alleles from animals of different farms in the central
coast of Peru, and subsequently determined three optimal human MHC-I and four optimal human MHC-II substitute alleles for
MHC-peptide prediction. The potential MHC restricted short peptide epitope-like candidates were predicted using human specific
(with determined suitable chicken substitutes) NetMHC MHC-peptide prediction model with web server features from all the
FAdV genomes available. FAdV specific peptides with calculated binding values to known substituted chicken MHC-I and MHC-II
were further filtered for diagnostics and potential vaccine epitopes. Promiscuity to the 3/4 optimal human MHC-I/II alleles and
conservation among the available FAdV genomes was considered in this analysis. The localization on the surface of the protein was
considered for class II predicted peptides. Thus, a set of class I and class II specific peptides from FAdV were reported in this study.
Hence, a multiepitopic protein was built with these peptides, and subsequently tested to confirm the production of specific
antibodies in chicken. 相似文献