全文获取类型
收费全文 | 2876篇 |
免费 | 206篇 |
出版年
2023年 | 17篇 |
2022年 | 22篇 |
2021年 | 33篇 |
2020年 | 38篇 |
2019年 | 37篇 |
2018年 | 45篇 |
2017年 | 38篇 |
2016年 | 83篇 |
2015年 | 124篇 |
2014年 | 145篇 |
2013年 | 151篇 |
2012年 | 215篇 |
2011年 | 196篇 |
2010年 | 132篇 |
2009年 | 100篇 |
2008年 | 166篇 |
2007年 | 159篇 |
2006年 | 146篇 |
2005年 | 147篇 |
2004年 | 149篇 |
2003年 | 144篇 |
2002年 | 147篇 |
2001年 | 42篇 |
2000年 | 25篇 |
1999年 | 25篇 |
1998年 | 51篇 |
1997年 | 35篇 |
1996年 | 22篇 |
1995年 | 31篇 |
1994年 | 25篇 |
1993年 | 26篇 |
1992年 | 32篇 |
1991年 | 18篇 |
1990年 | 21篇 |
1989年 | 15篇 |
1988年 | 21篇 |
1987年 | 22篇 |
1986年 | 19篇 |
1985年 | 13篇 |
1984年 | 13篇 |
1982年 | 11篇 |
1981年 | 24篇 |
1980年 | 15篇 |
1979年 | 13篇 |
1978年 | 15篇 |
1977年 | 13篇 |
1976年 | 12篇 |
1972年 | 6篇 |
1969年 | 6篇 |
1968年 | 7篇 |
排序方式: 共有3082条查询结果,搜索用时 15 毫秒
991.
Paul D. Wes Amy Easton John Corradi Donna M. Barten Nino Devidze Lynn B. DeCarr Amy Truong Aiqing He Nestor X. Barrezueta Craig Polson Clotilde Bourin Marianne E. Flynn Stefanie Keenan Regina Lidge Jere Meredith Joanne Natale Sethu Sankaranarayanan Greg W. Cadelina Charlie F. Albright Angela M. Cacace 《PloS one》2014,9(8)
Filamentous inclusions of the microtubule-associated protein, tau, define a variety of neurodegenerative diseases known as tauopathies, including Alzheimer’s disease (AD). To better understand the role of tau-mediated effects on pathophysiology and global central nervous system function, we extensively characterized gene expression, pathology and behavior of the rTg4510 mouse model, which overexpresses a mutant form of human tau that causes Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). We found that the most predominantly altered gene expression pathways in rTg4510 mice were in inflammatory processes. These results closely matched the causal immune function and microglial gene-regulatory network recently identified in AD. We identified additional gene expression changes by laser microdissecting specific regions of the hippocampus, which highlighted alterations in neuronal network activity. Expression of inflammatory genes and markers of neuronal activity changed as a function of age in rTg4510 mice and coincided with behavioral deficits. Inflammatory changes were tau-dependent, as they were reversed by suppression of the tau transgene. Our results suggest that the alterations in microglial phenotypes that appear to contribute to the pathogenesis of Alzheimer’s disease may be driven by tau dysfunction, in addition to the direct effects of beta-amyloid. 相似文献
992.
993.
Suzanne Arends Marianne Hofman Yvo PT Kamsma Eveline van der Veer Pieternella M Houtman Cees GM Kallenberg Anneke Spoorenberg Elisabeth Brouwer 《Arthritis research & therapy》2013,15(4):R99
Introduction
The aim of this study was to investigate the construct validity and test-retest reliability of the International Physical Activity Questionnaire (IPAQ; long form) and the Short QUestionnaire to Assess Health-enhancing physical activity (SQUASH) and to investigate the relation between daily physical activity and clinical assessments in patients with ankylosing spondylitis (AS).Methods
For validity, the self-report questionnaires IPAQ and SQUASH were compared with daily physical activity assessed with the ActiGraph accelerometer during 7 consecutive days in 63 AS outpatients. For reliability, the IPAQ and SQUASH were administered twice approximately 1 week apart in 52 AS outpatients. In all 115 patients, clinical assessments were performed at the outpatient clinic.Results
IPAQ and SQUASH total scores correlated significantly with accelerometer outcome: ρ = 0.38 and r = 0.35, respectively. Intraclass correlation coefficients between first and second assessments of the IPAQ and SQUASH were 0.83 and 0.89, respectively. Bland-Altman analyses showed no systemic bias, but in particular for the IPAQ the 95% limits of agreement were wide. Daily physical activity assessed by accelerometer, IPAQ, and SQUASH correlated significantly with disease activity, physical activity, and quality of life. A relation with spinal mobility was found only for the accelerometer and SQUASH. The direction of these correlations indicates that higher daily physical activity is related to lower disease activity and better physical function, spinal mobility and quality of life.Conclusions
Both physical activity questionnaires showed modest construct validity. The SQUASH showed good test-retest reliability, superior to the IPAQ. These results indicate that the SQUASH is more suitable than the IPAQ to assess daily physical activity in AS population studies. However, it is desirable to add questions on AS-specific physical activity. Further studies are needed to investigate the causality of the relation between daily physical activity and clinical assessments. 相似文献994.
Henner F. Farin Timo H-W. Lüdtke Martina K. Schmidt Susann Placzko Karin Schuster-Gossler Marianne Petry Vincent M. Christoffels Andreas Kispert 《PLoS genetics》2013,9(4)
Vertebrate limb outgrowth is driven by a positive feedback loop that involves Sonic hedgehog (Shh) and Gremlin1 (Grem1) in the posterior limb bud mesenchyme and Fibroblast growth factors (Fgfs) in the overlying epithelium. Proper spatio-temporal control of these signaling activities is required to avoid limb malformations such as polydactyly. Here we show that, in Tbx2-deficient hindlimbs, Shh/Fgf4 signaling is prolonged, resulting in increased limb bud size and duplication of digit 4. In turn, limb-specific Tbx2 overexpression leads to premature termination of this signaling loop with smaller limbs and reduced digit number as phenotypic manifestation. We show that Tbx2 directly represses Grem1 in distal regions of the posterior limb mesenchyme allowing Bone morphogenetic protein (Bmp) signaling to abrogate Fgf4/9/17 expression in the overlying epithelium. Since Tbx2 itself is a target of Bmp signaling, our data identify a growth-inhibiting positive feedback loop (Bmp/Tbx2/Grem1). We propose that proliferative expansion of Tbx2-expressing cells mediates self-termination of limb bud outgrowth due to their refractoriness to Grem1 induction. 相似文献
995.
Lotte Risom Marianne Dybdahl Peter MØller Håkan Wallin Terje Haug Ulla Vogel 《Free radical research》2013,47(2):172-181
DNA repair may prevent increased levels of oxidatively damaged DNA from prolonged oxidative stress induced by, e.g. exposure to diesel exhaust particles (DEP). We studied oxidative damage to DNA in broncho-alveolar lavage cells, lungs, and liver after 4 × 1.5 h inhalations of DEP (20 mg/m3) in Ogg1? / ? and wild type (WT) mice with similar extent of inflammation. DEP exposure increased lung levels of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) in Ogg1? / ? mice, whereas no effect on 8-oxodG or oxidized purines in terms of formamidopyrimidine DNA glycosylase (FPG) sites was observed in WT mice. In both unexposed and exposed Ogg1? / ? mice the level of FPG sites in the lungs was 3-fold higher than in WT mice. The high basal level of FPG sites in Ogg1? / ? mice probably saturated the assay and prevented detection of DEP-generated damage. In conclusion, Ogg1? / ? mice have elevated pulmonary levels of FPG sites and accumulate genomic 8-oxodG after repeated inhalations of DEP. 相似文献
996.
Delphine Judith Mehdi Bourai Nicolas Gangneux Mickaël Lelek Marianne Lucas‐Hourani Nadège Cayet Yves Jacob Marie‐Christine Prévost Philippe Pierre Frédéric Tangy Christophe Zimmer Pierre‐Olivier Vidalain Thérèse Couderc Marc Lecuit 《EMBO reports》2013,14(6):534-544
Chikungunya virus (CHIKV) is a recently re‐emerged arbovirus that triggers autophagy. Here, we show that CHIKV interacts with components of the autophagy machinery during its replication cycle, inducing a cytoprotective effect. The autophagy receptor p62 protects cells from death by binding ubiquitinated capsid and targeting it to autophagolysosomes. By contrast, the human autophagy receptor NDP52—but not its mouse orthologue—interacts with the non‐structural protein nsP2, thereby promoting viral replication. These results highlight the distinct roles of p62 and NDP52 in viral infection, and identify NDP52 as a cellular factor that accounts for CHIKV species specificity. 相似文献
997.
Anne Postec Marianne Quéméneur Aurélien Lecoeuvre Nicolas Chabert Manon Joseph Gaël Erauso 《Systematic and applied microbiology》2021,44(2):126175
Two novel anaerobic alkaliphilic strains, designated as LacTT and LacVT, were isolated from the Prony Bay Hydrothermal Field (PBHF, New Caledonia). Cells were motile, Gram-positive, terminal endospore-forming rods, displaying a straight to curved morphology during the exponential phase. Strains LacTT and LacVT were mesophilic (optimum 30 °C), moderately alkaliphilic (optimum pH 8.2 and 8.7, respectively) and halotolerant (optimum 2% and 2.5% NaCl, respectively). Both strains were able to ferment yeast extract, peptone and casamino acids, but only strain LacTT could use sugars (glucose, maltose and sucrose). Both strains disproportionated crotonate into acetate and butyrate. Phylogenetic analysis revealed that strains LacTT and LacVT shared 96.4% 16S rRNA gene sequence identity and were most closely related to A. peptidifermentans Z-7036, A. namsaraevii X-07-2 and A. hydrothermalis FatMR1 (95.7%–96.3%). Their genome size was of 3.29 Mb for strain LacTT and 3.06 Mb for strain LacVT with a G + C content of 36.0 and 33.9 mol%, respectively. The ANI value between both strains was 73.2 %. Finally, strains LacTT (=DSM 100337 = JCM 30643) and LacVT (=DSM 100017 = JCM 30644) are proposed as two novel species of the genus Alkaliphilus, order Clostridiales, phylum Firmicutes, Alkaliphilus serpentinus sp. nov. and Alkaliphilus pronyensis sp. nov., respectively. The genomes of the three Alkaliphilus species isolated from PBHF were consistently detected in the PBHF chimney metagenomes, although at very low abundance, but not significantly in the metagenomes of other serpentinizing systems (marine or terrestrial) worldwide, suggesting they represent indigenous members of the PBHF microbial ecosystem. 相似文献
998.
Gousy-Leblanc Marianne Yannic Glenn Therrien Jean-François Lecomte Nicolas 《Conservation Genetics》2021,22(5):685-702
Conservation Genetics - The current and rapid anthropogenic environmental changes could disproportionately impact ecosystems, particularly when they affect species with critical roles in ecosystem... 相似文献
999.
Jennyfer Levoux Alexandre Prola Peggy Lafuste Marianne Gervais Nathalie Chevallier Zeynab Koumaiha Kaouthar Kefi Laura Braud Alain Schmitt Azzedine Yacia Aurélie Schirmann Barbara Hersant Mounia Sid-Ahmed Sabrina Ben Larbi Katerina Komrskova Jakub Rohlena Frederic Relaix Jiri Neuzil Anne-Marie Rodriguez 《Cell metabolism》2021,33(3):688-690
1000.