全文获取类型
收费全文 | 2959篇 |
免费 | 179篇 |
专业分类
3138篇 |
出版年
2023年 | 14篇 |
2022年 | 39篇 |
2021年 | 57篇 |
2020年 | 36篇 |
2019年 | 75篇 |
2018年 | 69篇 |
2017年 | 53篇 |
2016年 | 89篇 |
2015年 | 164篇 |
2014年 | 140篇 |
2013年 | 208篇 |
2012年 | 243篇 |
2011年 | 209篇 |
2010年 | 136篇 |
2009年 | 101篇 |
2008年 | 173篇 |
2007年 | 179篇 |
2006年 | 169篇 |
2005年 | 162篇 |
2004年 | 158篇 |
2003年 | 132篇 |
2002年 | 151篇 |
2001年 | 22篇 |
2000年 | 16篇 |
1999年 | 28篇 |
1998年 | 21篇 |
1997年 | 19篇 |
1996年 | 23篇 |
1995年 | 19篇 |
1994年 | 16篇 |
1993年 | 14篇 |
1992年 | 11篇 |
1991年 | 19篇 |
1990年 | 9篇 |
1989年 | 9篇 |
1988年 | 10篇 |
1987年 | 12篇 |
1986年 | 6篇 |
1985年 | 6篇 |
1984年 | 12篇 |
1983年 | 10篇 |
1982年 | 21篇 |
1981年 | 9篇 |
1980年 | 7篇 |
1979年 | 9篇 |
1978年 | 5篇 |
1977年 | 10篇 |
1976年 | 5篇 |
1975年 | 4篇 |
1971年 | 4篇 |
排序方式: 共有3138条查询结果,搜索用时 0 毫秒
981.
Mauro Prato Chiara Magnetto Jithin Jose Amina Khadjavi Federica Cavallo Elena Quaglino Alice Panariti Ilaria Rivolta Emilio Benintende Gianfranco Varetto Monica Argenziano Adriano Troia Roberta Cavalli Caterina Guiot 《PloS one》2015,10(3)
Perfluoropentane (PFP)-based oxygen-loaded nanobubbles (OLNBs) were previously proposed as adjuvant therapeutic tools for pathologies of different etiology sharing hypoxia as a common feature, including cancer, infection, and autoimmunity. Here we introduce a new platform of oxygen nanocarriers, based on 2H,3H-decafluoropentane (DFP) as core fluorocarbon. These new nanocarriers have been named oxygen-loaded nanodroplets (OLNDs) since DFP is liquid at body temperature, unlike gaseous PFP. Dextran-shelled OLNDs, available either in liquid or gel formulations, display spherical morphology, ~600 nm diameters, anionic charge, good oxygen carrying capacity, and no toxic effects on human keratinocytes after cell internalization. In vitro OLNDs result more effective in releasing oxygen to hypoxic environments than former OLNBs, as demonstrated by analysis through oxymetry. In vivo, OLNDs effectively enhance oxy-hemoglobin levels, as emerged from investigation by photoacoustic imaging. Interestingly, ultrasound (US) treatment further improves transdermal oxygen release from OLNDs. Taken together, these data suggest that US-activated, DFP-based OLNDs might be innovative, suitable and cost-effective devices to topically treat hypoxia-associated pathologies of the cutaneous tissues. 相似文献
982.
Giulia Maria Camerino Jean-Fran?ois Desaphy Michela De Bellis Roberta Francesca Capogrosso Anna Cozzoli Maria Maddalena Dinardo Roberta Caloiero Kejla Musaraj Adriano Fonzino Elena Conte Catherine Jagerschmidt Florence Namour Antonella Liantonio Annamaria De Luca Diana Conte Camerino Sabata Pierno 《PloS one》2015,10(6)
Muscle disuse produces severe atrophy and a slow-to-fast phenotype transition in the postural Soleus (Sol) muscle of rodents. Antioxidants, amino-acids and growth factors were ineffective to ameliorate muscle atrophy. Here we evaluate the effects of nandrolone (ND), an anabolic steroid, on mouse skeletal muscle atrophy induced by hindlimb unloading (HU). Mice were pre-treated for 2-weeks before HU and during the 2-weeks of HU. Muscle weight and total protein content were reduced in HU mice and a restoration of these parameters was found in ND-treated HU mice. The analysis of gene expression by real-time PCR demonstrates an increase of MuRF-1 during HU but minor involvement of other catabolic pathways. However, ND did not affect MuRF-1 expression. The evaluation of anabolic pathways showed no change in mTOR and eIF2-kinase mRNA expression, but the protein expression of the eukaryotic initiation factor eIF2 was reduced during HU and restored by ND. Moreover we found an involvement of regenerative pathways, since the increase of MyoD observed after HU suggests the promotion of myogenic stem cell differentiation in response to atrophy. At the same time, Notch-1 expression was down-regulated. Interestingly, the ND treatment prevented changes in MyoD and Notch-1 expression. On the contrary, there was no evidence for an effect of ND on the change of muscle phenotype induced by HU, since no effect of treatment was observed on the resting gCl, restCa and contractile properties in Sol muscle. Accordingly, PGC1α and myosin heavy chain expression, indexes of the phenotype transition, were not restored in ND-treated HU mice. We hypothesize that ND is unable to directly affect the phenotype transition when the specialized motor unit firing pattern of stimulation is lacking. Nevertheless, through stimulation of protein synthesis, ND preserves protein content and muscle weight, which may result advantageous to the affected skeletal muscle for functional recovery. 相似文献
983.
Pseudomonas corrugata crpCDE is part of the cyclic lipopeptide corpeptin biosynthetic gene cluster and is involved in bacterial virulence in tomato and in hypersensitive response in Nicotiana benthamiana 下载免费PDF全文
984.
985.
Loren B. Andreas Jan Stanek Tanguy Le Marchand Andrea Bertarello Diane Cala-De Paepe Daniela Lalli Magdaléna Krejčíková Camille Doyen Carl Öster Benno Knott Sebastian Wegner Frank Engelke Isabella C. Felli Roberta Pierattelli Nicholas E. Dixon Lyndon Emsley Torsten Herrmann Guido Pintacuda 《Journal of biomolecular NMR》2015,62(3):253-261
986.
987.
Rizzo Claudia Vetro Roberta Vetro Angelo Mantia Roberto Iovane Angelo Di Gesù Marco Vasto Sonya Di Noto Laura Mazzola Giuseppina Caruso Calogero 《Immunity & ageing : I & A》2014,11(1):1-5
Background
Ageing affects many components of the immune system, including innate immune cells like monocytes. They are important in the early response to pathogens and for their role to differentiate into macrophages and dendritic cells. Recent studies have revealed significant age-related changes in genomic DNA methylation in peripheral blood mononuclear cells, however information on epigenetic changes in specific leukocyte subsets is still lacking. Here, we aimed to analyse DNA methylation in purified monocyte populations from young and elderly individuals.Findings
We analysed the methylation changes in monocytes purified from young and elderly individuals using the HumanMethylation450 BeadChip array. Interestingly, we found that among 26 differentially methylated CpG sites, the majority of sites were hypomethylated in elderly individuals. The most hypomethylated CpG sites were located in neuropilin 1 (NRP1; cg24892069) and neurexin 2 (NRXN2; cg27209729) genes, and upstream of miR-29b-2 gene (cg10501210). The age-related hypomethylation of these three sites was confirmed in a separate group of young and elderly individuals.Conclusions
We identified significant age-related hypomethylation in human purified monocytes at CpG sites within the regions of NRP1, NRXN2 and miR-29b-2 genes. 相似文献988.
Claudia SEBBIO Claudio CARERE Giuseppe NASCETTI Bruno BELLISARIO Pasquale MOSESSO Roberta CIMMARUTA Dario ANGELETTI 《动物学报(英文版)》2014,(2):308-321
The choice of a suitable species to translate pollution signals into a quantitative monitor is a fundamental step in biomonitoring plans. Here we present the results of three years of biomonitoring at a new coal power plant in central Italy using three different aquatic and terrestrial wildlife species in order to compare their reliability as sentinel organisms for genotoxicity. The comet assay was applied to the common land snail Helix spp., the lagoon fish Aphaniusfasciatus, and the green frog Rana esculenta sampled in the area potentially exposed to the impact of the power station. The tissue concentration of some expected pollutants (As, Cd, Ni, Pb, Cr) was analysed in parallel samples collected in the same sampling sites. The three species showed different values in the comet assay (Tail Intensity) and different accumulation profiles of heavy metals. Aphanius fasciatus showed an increasing genotoxic effect over time that paralleled the temporal increase of the heavy metals, especially arsenic, and the highest correlation between heavy metals and DNA damage. Helix spp. showed levels of damage inversely related to the distance from the source of pollution and in partial accordance with the total accumulation of trace elements. On the contrary, Rana esculenta showed a low capability to accumulate metals and had inconsistent results in the comet test. The fish appeared to be the most efficient and sensitive species in detecting chemical pollution. Overall, both the fish and the snail reflected a trend of increasing pollution in the area surrounding the power plant across time and space [Current Zoology 60 (2): 308-321, 2014]. 相似文献
989.
Prenatal diagnosis of proximal partial trisomy 1q confirmed by comparative genomic hybridization array: Molecular cytogenetic analysis,fetal pathology and review of the literature 下载免费PDF全文
990.
Maria Teresa Pallotta Ciriana Orabona Roberta Bianchi Carmine Vacca Francesca Fallarino Maria Laura Belladonna Claudia Volpi Giada Mondanelli Marco Gargaro Massimo Allegrucci Vincenzo Nicola Talesa Paolo Puccetti Ursula Grohmann 《Journal of cellular and molecular medicine》2014,18(10):2082-2091
Indoleamine 2,3‐dioxygenase (IDO1), a tryptophan catabolizing enzyme, is recognized as an authentic regulator of immunity in several physiopathologic conditions. We have recently demonstrated that IDO1 does not merely degrade tryptophan and produce immunoregulatory kynurenines, but it also acts as a signal‐transducing molecule, independently of its enzymic function. IDO1 signalling activity is triggered in plasmacytoid dendritic cells (pDCs) by transforming growth factor‐β (TGF‐β), an event that requires the non‐canonical NF‐κB pathway and induces long‐lasting IDO1 expression and autocrine TGF‐β production in a positive feedback loop, thus sustaining a stably regulatory phenotype in pDCs. IDO1 expression and catalytic function are defective in pDCs from non‐obese diabetic (NOD) mice, a prototypic model of autoimmune diabetes. In the present study, we found that TGF‐β failed to activate IDO1 signalling function as well as up‐regulate IDO1 expression in NOD pDCs. Moreover, TGF‐β‐treated pDCs failed to exert immunosuppressive properties in vivo. Nevertheless, transfection of NOD pDCs with Ido1 prior to TGF‐β treatment resulted in activation of the Ido1 promoter and induction of non‐canonical NF‐κB and TGF‐β, as well as decreased production of the pro‐inflammatory cytokines, interleukin 6 (IL‐6) and tumour necrosis factor‐α (TNF‐α). Overexpression of IDO1 in TGF‐β‐treated NOD pDCs also resulted in pDC ability to suppress the in vivo presentation of a pancreatic β‐cell auto‐antigen. Thus, our data suggest that a correction of IDO1 expression may restore its dual function and thus represent a proper therapeutic manoeuvre in this autoimmune setting. 相似文献