全文获取类型
收费全文 | 1040篇 |
免费 | 60篇 |
国内免费 | 1篇 |
专业分类
1101篇 |
出版年
2024年 | 1篇 |
2023年 | 5篇 |
2022年 | 13篇 |
2021年 | 33篇 |
2020年 | 28篇 |
2019年 | 27篇 |
2018年 | 36篇 |
2017年 | 15篇 |
2016年 | 56篇 |
2015年 | 60篇 |
2014年 | 65篇 |
2013年 | 78篇 |
2012年 | 97篇 |
2011年 | 88篇 |
2010年 | 44篇 |
2009年 | 59篇 |
2008年 | 55篇 |
2007年 | 63篇 |
2006年 | 57篇 |
2005年 | 42篇 |
2004年 | 33篇 |
2003年 | 30篇 |
2002年 | 22篇 |
2001年 | 9篇 |
2000年 | 7篇 |
1999年 | 9篇 |
1998年 | 10篇 |
1997年 | 3篇 |
1996年 | 3篇 |
1995年 | 9篇 |
1994年 | 7篇 |
1993年 | 2篇 |
1992年 | 7篇 |
1991年 | 3篇 |
1990年 | 2篇 |
1989年 | 3篇 |
1988年 | 3篇 |
1987年 | 3篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1973年 | 2篇 |
1967年 | 1篇 |
1962年 | 1篇 |
1951年 | 1篇 |
排序方式: 共有1101条查询结果,搜索用时 15 毫秒
1.
J L Thomas E A Berko A Faustino R P Myers R C Strickler 《Journal of steroid biochemistry》1988,31(5):785-793
In human pregnancy, placental 3 beta-hydroxy-5-ene-steroid dehydrogenase and steroid 5----4-ene-isomerase produce progesterone from pregnenolone and metabolize fetal dehydroepiandrosterone sulfate to androstenedione, an estrogen precursor. The enzyme complex was solubilized from human placental microsomes using the anionic detergent, sodium cholate. Purification (500-fold, 3.9% yield) was achieved by ion exchange chromatography (Fractogel-TSK DEAE 650-S) followed by hydroxylapatite chromatography (Bio-Gel HT). The purified enzyme was detected as a single protein band in sodium dodecylsulfate-polyacrylamide gel electrophoresis (monomeric Mr = 19,000). Fractionation by gel filtration chromatography at constant specific enzyme activity supported enzyme homogeneity and determined the molecular mass (Mr = 76,000). The dehydrogenase and isomerase activities copurified. Kinetic constants were determined at pH 7.4, 37 degrees C for the oxidation of pregnenolone (Km = 1.9 microM, Vmax = 32.6 nmol/min/mg) and dehydroepiandrosterone (Km = 2.8 microM, Vmax = 32.0 nmol/min/mg) and for the isomerization of 5-pregnene-3,20-dione (Km = 9.7 microM, Vmax = 618.3 nmol/min/mg) and 5-androstene-3,17-dione (Km = 23.7 microM, Vmax = 625.7 nmol/min/mg). Mixed substrate analyses showed that the dehydrogenase and isomerase reactions use the appropriate pregnene and androstene steroids as alternative, competitive substrates. Dixon analyses demonstrated competitive inhibition of the oxidation of pregnenolone and dehydroepiandrosterone by both product steroids, progesterone and androstenedione. The enzyme has a 3-fold higher affinity for androstenedione than for progesterone as an inhibitor of dehydrogenase activity. Based on these competitive patterns of substrate utilization and product inhibition, the pregnene and androstene activities of 3 beta-hydroxy-5-ene-steroid dehydrogenase and steroid 5----4-ene-isomerase may be expressed at a single catalytic site on one protein in human placenta. 相似文献
2.
3.
Mayrel Palestino-Domínguez Alejandro Escobedo-Calvario Soraya Salas-Silva Moises Vergara-Mendoza Veronica Souza-Arroyo Roberto Lazzarini Roxana Miranda-Labra Leticia Bucio-Ortiz María Concepción Gutiérrez-Ruiz Luis E. Gomez-Quiroz 《Journal of biochemical and molecular toxicology》2023,37(4):e23302
Alcohol-induced pancreas damage remains as one of the main risk factors for pancreatitis development. This disorder is poorly understood, particularly the effect of acetaldehyde, the primary alcohol metabolite, in the endocrine pancreas. Hepatocyte growth factor (HGF) is a protective protein in many tissues, displaying antioxidant, antiapoptotic, and proliferative responses. In the present work, we were focused on characterizing the response induced by HGF and its protective mechanism in the RINm5F pancreatic cell line treated with ethanol and acetaldehyde. RINm5F cells were treated with ethanol or acetaldehyde for 12 h in the presence or not of HGF (50 ng/ml). Cells under HGF treatment decreased the content of reactive oxygen species and lipid peroxidation induced by both toxics, improving cell viability. This effect was correlated to an improvement in insulin expression impaired by ethanol and acetaldehyde. Using a specific inhibitor of Erk1/2 abrogated the effects elicited by the growth factor. In conclusion, the work provides mechanistic evidence of the HGF-induced-protective response to the alcohol-induced damage in the main cellular component of the endocrine pancreas. 相似文献
4.
The membrane-bound ATPase activity from two substrains ofMicrococcus lysodeikticus, designated as A and B, was inhibited by antibodies raised against the two forms of purified F1-ATPase. Form B of the enzyme, which behaved as a poorer immunogen than form A, also showed less reactivity as an antigen, independent of the physical state of the F1-ATPase form. Antibodies were raised against the two major subunits ( and ) isolated fromM. lysodeikticus F1-ATPase form A, which was the most stable form of the enzyme. Anti-(-subunit) serum strongly inhibited the ATPase activity of membrane-bound ATPase but showed little inhibition of the purified, soluble F1-ATPase. The anti-(-subunit) serum inhibited the soluble F1-ATPase, but to a lesser extent than the membrane-bound enzyme. In any event, the effect of anti- antibodies on the membrane-bound ATPase was smaller than that of anti- antibodies. It was postulated that the subunit ofM. lysodeikticus F1-ATPase plays an essential and regulatory role in the expression of the immunochemical properties of the protein. 相似文献
5.
Israel F. Costa Gilvan P. Pires Jos Geraldo P. Espínola Hermi F. Brito Maria Claudia F.C. Felinto Wagner M. Faustino Ercules E.S. Teotonio 《Luminescence》2020,35(3):365-372
This paper reports on the preparation, characterization, and photoluminescence properties of novel hybrid materials, in which the EDTA–Ln–L complexes (where L: H2O, acac, bzac, dbm, and tta ligands, and Ln: Eu, Gd, and Tb) were covalently linked to the precursor medium molecular weight chitosan surface (CS) matrices or on the chitosan surfaces previously crosslinked with epichlorohydrin (CSech). The emission spectra of these materials were characterized by intraconfigurational‐4fN transitions centred on the Eu3+ and Tb3+ ions. Some broad bands from the polymeric matrix were also observed in the emission spectra, however the relative intensities of the intraconfigurational bands increased significantly for systems containing diketonate ligands when the antenna effect became more efficient. The values of the radiative rates (Arad) were higher for crosslinked hybrid systems with epichlorohydrin, while nonradiative rates (Anrad) presented the opposite behaviour. These data contributed to an increase in the values of emission quantum efficiency (η) for crosslinked materials. The effect of the modification process and antenna ligand on the values of intensities, intensity parameters Ω2 e Ω4 of the Eu3+ complexes were also investigated. The results showed that the crosslinked biopolymer surfaces have great potential for applications in molecular devices light converters. 相似文献
6.
dos Santos Fernanda Marcelia Pflüger Pricila Fernandes Lazzarotto Leticia Uczay Mariana de Aguida Wesley Roberto da Silva Lisiane Santos Boaretto Fernanda Brião Menezes de Sousa Jayne Torres Picada Jaqueline Nascimento da Silva Torres Iraci Lucena Pereira Patrícia 《Neurochemical research》2021,46(8):2066-2078
Neurochemical Research - Gamma-decanolactone (GD) has been shown to reduce epileptic behavior in different models, inflammatory decreasing, oxidative stress, and genotoxic parameters. This study... 相似文献
7.
Joana M. Andrade Eva María Domínguez-Martín Marisa Nicolai Clia Faustino Luís Monteiro Rodrigues Patrícia Rijo 《Journal of enzyme inhibition and medicinal chemistry》2021,36(1):258
A series of Plectranthus spp. plant extracts (aqueous, acetonic, methanolic and ethyl acetic) obtained from eight different species, and previously isolated compounds (ranging from polyphenols, diterpenes and triterpenes), were assayed for in vitro inhibition of the skin-related enzymes tyrosinase, collagenase and elastase, and for studying their antioxidant properties. The ethyl acetic extracts of P. grandidentatus and P. ecklonii registered the highest antioxidant activity, whereas acetonic, methanolic and ethyl acetic extracts of P. ecklonii, P. grandidentatus, P. madagascariensis and P. saccatus concerning the enzymatic inhibition assays revealed high anti-tyrosinase and anti-collagenase activities. From the isolated compounds tested, abietane diterpenes and triterpenes were highly active against tyrosinase and elastase activity. Overall, the experimental results showed the powerful antioxidant and inhibitory action on skin-related enzymes tyrosinase, collagenase and elastase of Plectranthus spp. extracts and/or isolated compounds, supporting their further research as bioactive metabolites against skin sagging and hyperpigmentation in cosmetic and pharmaceutical formulations. 相似文献
8.
Aline Queiroz Emmanuel Albuquerque-Souza Leticia Miquelitto Gasparoni Bruno Nunes de Fran a Cibele Pelissari Mar lia Trierveiler Marinella Holzhausen 《World journal of stem cells》2021,13(6):605-618
Inflammatory periodontal disease known as periodontitis is one of the most common conditions that affect human teeth and often leads to tooth loss. Due to the complexity of the periodontium, which is composed of several tissues, its regeneration and subsequent return to a homeostatic state is challenging with the therapies currently available. Cellular therapy is increasingly becoming an alternative in regenerative medicine/dentistry, especially therapies using mesenchymal stem cells, as they can be isolated from a myriad of tissues. Periodontal ligament stem cells (PDLSCs) are probably the most adequate to be used as a cell source with the aim of regenerating the periodontium. Biological insights have also highlighted PDLSCs as promising immunomodulator agents. In this review, we explore the state of knowledge regarding the properties of PDLSCs, as well as their therapeutic potential, describing current and future clinical applications based on tissue engineering techniques. 相似文献
9.
Chamaida Plasencia Dora Pascual-Salcedo Sara García-Carazo Leticia Lojo Laura Nu?o Alejandro Villalba Diana Peiteado Florencia Arribas Jesus Díez Maria Teresa López-Casla Emilio Martín-Mola Alejandro Balsa 《Arthritis research & therapy》2013,15(4):R79
Introduction
Anti-TNF drugs have proven to be effective against spondyloarthritis (SpA), although 30% of patients fail to respond or experience adverse events leading to treatment discontinuation. In rheumatoid arthritis, the presence of anti-drug antibodies (ADA) against the first TNF inhibitor influences the outcome after switching. Our aim was to assess whether the response to a second anti-TNF drug is related to the previous development of ADA to the first anti-TNF drug SpA patients.Methods
Forty-two SpA patients began a second anti-TNF drug after failing to respond to the first anti-TNF therapy. Clinical activity was assessed by the Ankylosing Spondylitis Disease Activity Score (ASDAS) at baseline (at the beginning of the first and second anti-TNF therapy) and at 6 months after switching. The drug and ADA levels were measured by ELISA before each administration.Results
All patients were treated with anti-TNF drugs and mainly due to inefficacy were switched to a second anti-TNF drug. Eleven of 42 (26.2%) developed ADA during the first biologic treatment. At baseline, no differences in ASDAS were found in patients with or without ADA to the first anti-TNF drug (3.52 ± 1.03 without ADA vs. 3.14 ± 0.95 with ADA, p = 0.399) and to the second anti-TNF drug (3.36 ± 0.94 without ADA vs. 3.09 ± 0.91 with ADA, p = 0.466). At 6 months after switching, patients with previous ADA had lower disease activity (1.62 ± 0.93 with ADA vs. 2.79 ± 1.01 without ADA, p = 0.002) and most patients without ADA had high disease activity state by the ASDAS (25 out of 31 (80.6%) without ADA vs. 3 out of 11 (27.3%) with ADA, p = 0.002).Conclusions
In SpA the failure to respond to the first anti-TNF drug due to the presence of ADA predicts a better clinical response to a second anti-TNF drug. 相似文献10.