全文获取类型
收费全文 | 5495篇 |
免费 | 507篇 |
国内免费 | 2篇 |
专业分类
6004篇 |
出版年
2024年 | 5篇 |
2023年 | 45篇 |
2022年 | 92篇 |
2021年 | 212篇 |
2020年 | 103篇 |
2019年 | 157篇 |
2018年 | 192篇 |
2017年 | 144篇 |
2016年 | 229篇 |
2015年 | 405篇 |
2014年 | 359篇 |
2013年 | 382篇 |
2012年 | 523篇 |
2011年 | 488篇 |
2010年 | 293篇 |
2009年 | 210篇 |
2008年 | 328篇 |
2007年 | 330篇 |
2006年 | 294篇 |
2005年 | 258篇 |
2004年 | 227篇 |
2003年 | 224篇 |
2002年 | 185篇 |
2001年 | 30篇 |
2000年 | 26篇 |
1999年 | 40篇 |
1998年 | 46篇 |
1997年 | 21篇 |
1996年 | 14篇 |
1995年 | 18篇 |
1994年 | 13篇 |
1993年 | 8篇 |
1992年 | 9篇 |
1991年 | 6篇 |
1990年 | 9篇 |
1988年 | 4篇 |
1986年 | 6篇 |
1985年 | 4篇 |
1983年 | 3篇 |
1982年 | 3篇 |
1981年 | 5篇 |
1980年 | 5篇 |
1977年 | 4篇 |
1973年 | 5篇 |
1969年 | 3篇 |
1967年 | 5篇 |
1963年 | 2篇 |
1962年 | 2篇 |
1957年 | 2篇 |
1950年 | 2篇 |
排序方式: 共有6004条查询结果,搜索用时 7 毫秒
71.
Hay DC Pernagallo S Diaz-Mochon JJ Medine CN Greenhough S Hannoun Z Schrader J Black JR Fletcher J Dalgetty D Thompson AI Newsome PN Forbes SJ Ross JA Bradley M Iredale JP 《Stem cell research》2011,6(2):92-102
Maintaining stable differentiated somatic cell function in culture is essential to a range of biological endeavors. However, current technologies, employing, for example, primary hepatic cell culture (essential to the development of a bio-artificial liver and improved drug and toxicology testing), are limited by supply, expense, and functional instability even on biological cell culture substrata. As such, novel biologically active substrates manufacturable to GMP standards have the potential to improve cell culture-based assay applications. Currently hepatic endoderm (HE) generated from pluripotent stem cells is a genotypically diverse, cheap, and stable source of "hepatocytes"; however, HE routine applications are limited due to phenotypic instability in culture. Therefore a manufacturable subcellular matrix capable of supporting long-term differentiated cell function would represent a step forward in developing scalable and phenotypically stable hESC-derived hepatocytes. Adopting an unbiased approach we screened polymer microarrays and identified a polyurethane matrix which promoted HE viability, hepatocellular gene expression, drug-inducible metabolism, and function. Moreover, the polyurethane supported, when coated on a clinically approved bio-artificial liver matrix, long-term hepatocyte function and growth. In conclusion, our data suggest that an unbiased screening approach can identify cell culture substrate(s) that enhance the phenotypic stability of primary and stem cell-derived cell resources. 相似文献
72.
73.
74.
Rebeca Saborido Nazareth Martinón Alexandra Regueiro Vanesa Crujeiras Pablo Eiras Rosaura Leis 《Journal of physiology and biochemistry》2018,74(1):153-158
According to new ESPGHAN guidelines, gluten challenge is considered necessary when there is doubt about the initial diagnosis of celiac disease (CD). The main aim of this study was to quantify intraepithelial lymphocyte (IEL) immunophenotype on celiac patients on gluten-containing diet (GCD) compared to those on gluten-free diet (GFD). Another aim was to evaluate the clinical utility of IELs in the CD diagnosis, especially in selected patients on GFD where diagnostic uncertainty remains. IEL immunophenotype (TCRγδ and NK-like IELs) were studied by flow cytometry in 111 children with CD (81 children with CD on GCD and 30 celiac patients on GFD) and a control group (10 children). Duration of GFD was 5.4 ± 1.6 years. TCRγδ IELs in celiac patients receiving a GCD or GFD were significantly higher (p < 0.001) than in the control group. NK-like IELs in patients receiving a GCD or GFD were significantly lower than in the control group (p < 0.001). We observed a permanent decrease of NK-like IELs and an increment of TCRγδ IELs after following an adequate establishment and compliance of a long-term GFD in celiac patients. Recognition of IELs changes in the intestinal mucosa on celiac patients after long-term establishment of a GFD could constitute a useful tool for CD diagnosis in various situations: in which there is doubt about the initial diagnosis and repeat biopsy is necessary (avoiding the need of gluten challenges), and in those patients with symptoms/signs suggestive of CD who maintain a low gluten diet. 相似文献
75.
Shen-Ying Zhang Nathaniel E. Clark Catherine A. Freije Elodie Pauwels Allison J. Taggart Satoshi Okada Hanna Mandel Paula Garcia Michael J. Ciancanelli Anat Biran Fabien G. Lafaille Miyuki Tsumura Aurélie Cobat Jingchuan Luo Stefano Volpi Bastian Zimmer Sonoko Sakata Alexandra Dinis Jean-Laurent Casanova 《Cell》2018,172(5):952-965.e18
76.
Lactuca capensis reverses memory deficits in Aβ1‐42‐induced an animal model of Alzheimer's disease 下载免费PDF全文
Paula Alexandra Postu Jaures A. K. Noumedem Oana Cioanca Monica Hancianu Marius Mihasan Mitica Ciorpac Dragos Lucian Gorgan Brindusa Alina Petre Lucian Hritcu 《Journal of cellular and molecular medicine》2018,22(1):111-122
We investigated the neuropharmacological effects of the methanolic extract from Lactuca capensis Thunb. leaves (100 and 200 mg/kg) for 21 days on memory impairment in an Alzheimer's disease (AD) rat model produced by direct intraventricular delivery of amyloid‐β1‐42 (Aβ1‐42). Behavioural assays such as Y‐maze and radial arm maze test were used for assessing memory performance. Aβ1‐42 decreased cognitive performance in the behavioural tests which were ameliorated by pre‐treatment with the methanolic extract. Acetylcholinesterase activity and oxidant–antioxidant balance in the rat hippocampus were abnormally altered by Aβ1‐42 treatment while these deficits were recovered by pre‐treatment with the methanolic extract. In addition, rats were given Aβ1‐42 exhibited in the hippocampus decreased brain‐derived neurotrophic factor (BDNF) mRNA copy number and increased IL‐1β mRNA copy number which was reversed by the methanolic extract administration. These findings suggest that the methanolic extract could be a potent neuropharmacological agent against dementia via modulating cholinergic activity, increasing of BDNF levels and promoting antioxidant action in the rat hippocampus. 相似文献
77.
78.
79.
Eric G. Hernández Julio Granados Oswaldo Partida-Rodríguez Olivia Valenzuela Edgar Rascón Ulises Maga?a Mónica Escamilla-Tilch Alberto López-Reyes Miriam Nieves-Ramírez Enrique González Patricia Morán Liliana Rojas Alicia Valadez Alexandra Luna Francisco J. Estrada Carmen Maldonado Cecilia Ximénez 《PloS one》2015,10(5)
Amebiasis is an endemic disease and a public health problem throughout Mexico, although the incidence rates of amebic liver abscess (ALA) vary among the geographic regions of the country. Notably, incidence rates are high in the northwestern states (especially Sonora with a rate of 12.57/100,000 inhabitants) compared with the central region (Mexico City with a rate of 0.69/100,000 inhabitants). These data may be related to host genetic factors that are partially responsible for resistance or susceptibility. Therefore, we studied the association of the HLA-DRB1 and HLA-DQB1 alleles with resistance or susceptibility to ALA in two Mexican populations, one each from Mexico City and Sonora. Ninety ALA patients were clinically diagnosed by serology and sonography. Genomic DNA was extracted from peripheral blood mononuclear cells. To establish the genetic identity of both populations, 15 short tandem repeats (STRs) were analyzed with multiplexed PCR, and the allelic frequencies of HLA were studied by PCR-SSO using LUMINEX technology. The allele frequencies obtained were compared to an ethnically matched healthy control group (146 individuals). We observed that both affected populations differed genetically from the control group. We also found interesting trends in the population from Mexico City. HLA-DQB1*02 allele frequencies were higher in ALA patients compared to the control group (0.127 vs 0.047; p= 0.01; pc= NS; OR= 2.9, 95% CI= 1.09-8.3). The less frequent alleles in ALA patients were HLA-DRB1*08 (0.118 vs 0.238 in controls; p= 0.01; pc= NS; OR= 0.42, 95% CI= 0.19-0.87) and HLA-DQB1*04 (0.109 vs 0.214; p= 0.02; pc= NS; OR= 0.40, 95% CI= 0.20-0.94). The haplotype HLA-DRB1*08/-DQB1*04 also demonstrated a protective trend against the development of this disease (0.081 vs. 0.178; p=0.02; pc=NS; OR= 0.40, 95% CI= 0.16-0.93). These trends suggest that the prevalent alleles in the population of Mexico City may be associated with protection against the development of ALA. 相似文献
80.
Nikita A. Kuznetsov Nicolai G. Faleev Alexandra A. Kuznetsova Elena A. Morozova Svetlana V. Revtovich Natalya V. Anufrieva Alexei D. Nikulin Olga S. Fedorova Tatyana V. Demidkina 《The Journal of biological chemistry》2015,290(1):671-681
Methionine γ-lyase (MGL) catalyzes the γ-elimination of l-methionine and its derivatives as well as the β-elimination of l-cysteine and its analogs. These reactions yield α-keto acids and thiols. The mechanism of chemical conversion of amino acids includes numerous reaction intermediates. The detailed analysis of MGL interaction with glycine, l-alanine, l-norvaline, and l-cycloserine was performed by pre-steady-state stopped-flow kinetics. The structure of side chains of the amino acids is important both for their binding with enzyme and for the stability of the external aldimine and ketimine intermediates. X-ray structure of the MGL·l-cycloserine complex has been solved at 1.6 Å resolution. The structure models the ketimine intermediate of physiological reaction. The results elucidate the mechanisms of the intermediate interconversion at the stages of external aldimine and ketimine formation. 相似文献