全文获取类型
收费全文 | 1062篇 |
免费 | 80篇 |
专业分类
1142篇 |
出版年
2024年 | 1篇 |
2023年 | 9篇 |
2022年 | 21篇 |
2021年 | 26篇 |
2020年 | 19篇 |
2019年 | 27篇 |
2018年 | 44篇 |
2017年 | 34篇 |
2016年 | 55篇 |
2015年 | 66篇 |
2014年 | 84篇 |
2013年 | 78篇 |
2012年 | 120篇 |
2011年 | 88篇 |
2010年 | 59篇 |
2009年 | 45篇 |
2008年 | 76篇 |
2007年 | 49篇 |
2006年 | 47篇 |
2005年 | 42篇 |
2004年 | 50篇 |
2003年 | 39篇 |
2002年 | 30篇 |
2001年 | 4篇 |
2000年 | 4篇 |
1999年 | 7篇 |
1998年 | 5篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1992年 | 1篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1974年 | 1篇 |
排序方式: 共有1142条查询结果,搜索用时 15 毫秒
851.
TL Morelli AB Smith CR Kastely I Mastroserio C Moritz SR Beissinger 《Proceedings. Biological sciences / The Royal Society》2012,279(1745):4279-4286
We conducted detailed resurveys of a montane mammal, Urocitellus beldingi, to examine the effects of climate change on persistence along the trailing edge of its range. Of 74 California sites where U. beldingi were historically recorded (1902-1966), 42 per cent were extirpated, with no evidence for colonization of previously unoccupied sites. Increases in both precipitation and temperature predicted site extirpations, potentially owing to snowcover loss. Surprisingly, human land-use change buffered climate change impacts, leading to increased persistence and abundance. Excluding human-modified sites, U. beldingi has shown an upslope range retraction of 255 m. Generalized additive models of past distribution were predictive of modern range contractions (AUC = 0.76) and projected extreme reductions (52% and 99%, respectively) of U. beldingi's southwestern range to 2080 climates (Hadley and CCCMA A2). Our study suggests the strong impacts of climate change on montane species at their trailing edge and how anthropogenic refugia may mitigate these effects. 相似文献
852.
853.
Rosanna Capparelli Ilaria Ventimiglia Luigi Longobardo Domenico Iannelli 《Cytometry. Part A》2005,63(2):108-113
BACKGROUND: Celiac disease is a widely prevalent enteropathy caused by intolerance to gliadin, one of the gluten proteins. We developed two methods for the analysis of gliadin levels. Both methods use flow cytometry and rat antibodies against a 16-residue peptide of gliadin. The peptide is common to the alpha-, beta-, gamma-, and omega-gliadins. METHODS: In the one-site assay, the antigen (gliadin standard or food extract) was adsorbed on 3-mum latex particles. Sensitized particles were then incubated, in this order, with rat anti-gliadin peptide antibodies and anti-rat immunoglobulin G antibodies labeled with fluorescein isothiocyanate. In the two-site assay, the antigen was trapped on the latex particles by rat anti-gliadin antibodies and then measured by the same antibodies labeled with fluorescein. RESULTS: Detection limits were 1 ng/ml for the one-site assay and 10 pg/ml for the two-site assay. The two-site assay displayed gliadin at concentrations above the limit proposed by the Codex Alimentarius in 2 of 40 gluten-free products. CONCLUSION: There is a growing concern that gliadin, even when present in gluten-free foods within the limit fixed by the Codex Alimentarius, over the long term may become toxic to patients with celiac disease. The techniques described in this study provide an opportunity to further decrease the acceptable limit of gliadin in gluten-free foods. 相似文献
854.
Ceglia I Carli M Baviera M Renoldi G Calcagno E Invernizzi RW 《Journal of neurochemistry》2004,91(1):189-199
We recently found that intracortical injection of the selective and competitive N-methyl-D-aspartate (NMDA) receptor antagonist 3-(R)-2-carboxypiperazin-4-propyl-1-phosphonic acid (CPP) impaired attentional performance in rats and blockade of 5-hydroxytryptamine (5-HT)2A receptors antagonized this effect. Here, we used the microdialysis technique in conscious rats to study the effect of CPP on extracellular glutamate (GLU) in the medial prefrontal cortex (mPFC) and the regulation of this effect by 5-HT2A receptors. Intraperitoneal injection of 20 mg/kg CPP increased extracellular GLU in the mPFC (201% of basal levels) but had no effect on 5-HT. Intracortical infusion of 100 microm CPP increased extracellular GLU (230% of basal values) and 5-HT (150% of basal values) in the mPFC, whereas 30 microm had no significant effect. The effect of 100 microm CPP on extracellular GLU was abolished by tetrodotoxin, suggesting that neuronal activity is required. Subcutaneous injection of 40 microg/kg M100,907 completely antagonized the effect of 100 microm cpp on extracellular GLU, whereas 10 microg/kg caused only partial attenuation. Likewise, intracortical infusion of 0.1 microm M100,907 completely reversed the increase of extracellular GLU induced by CPP. These findings show that blockade of NMDA receptors in the mPFC is sufficient to increase extracellular GLU locally. The increase of cortical extracellular GLU may contribute to CPP-induced cognitive deficits and blockade of 5-HT2A receptors may provide a molecular mechanism for reversing these deficits caused by dysfunctional glutamatergic transmission in the mPFC. 相似文献
855.
Maria Serena Piccinno Elena Veronesi Pietro Loschi Marco Pignatti Alba Murgia Giulia Grisendi Ilaria Castelli Daniela Bernabei Olivia Candini Pierfranco Conte Paolo Paolucci Edwin M. Horwitz Giorgio De Santis Lorenzo Iughetti Massimo Dominici 《Apoptosis : an international journal on programmed cell death》2013,18(10):1274-1289
Autologous fat transfer (AFT) is a procedure for adipose tissue (AT) repair after trauma, burns, post-tumor resections and lipodystrophies still negatively impacted by the lack of graft persistence. The reasons behind this poor outcome are unclear and seem to involve damages in either harvested/transplanted mature adipocytes or on their mesenchymal progenitors, namely adipose stromal/stem cells (ASC), and due to post-transplant AT apoptosis and involution. A rabbit subcutaneous AT regeneration model was here developed to first evaluate graft quality at different times after implant focusing on related parameters, such as necrosis and vasculogenesis. Standard AFT was compared with a strategy where purified autologous ASC, combined with hyaluronic acid (HA), assisted AFT. Five million of autologous ex vivo isolated CD29+, CD90+, CD49e+ ASC, loaded into HA, enriched 1 ml of AT generating an early significant protective effect in reducing AFT necrosis and increasing vasculogenesis with a preservation of transplanted AT architecture. This beneficial impact of ASC assisted AFT was then confirmed at three months with a robust lipopreservation and no signs of cellular transformation. By a novel ASC assisted AFT approach we ensure a reduction in early cell death favoring an enduring graft performance possibly for a more stable benefit in patients. 相似文献
856.
Francesca Massenzio Emiliano Peña-Altamira Sabrina Petralla Marco Virgili Giampaolo Zuccheri Andrea Miti Elisabetta Polazzi Ilaria Mengoni Deborah Piffaretti Barbara Monti 《生物化学与生物物理学报:疾病的分子基础》2018,1864(12):3771-3785
Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease. Mutations in the gene encoding copper/zinc superoxide dismutase-1 (SOD1) are responsible for most familiar cases, but the role of mutant SOD1 protein dysfunction in non-cell autonomous neurodegeneration, especially in relation to microglial activation, is still unclear. Here, we focused our study on microglial cells, which release SOD1 also through exosomes. We observed that in rat primary microglia the overexpression of the most-common SOD1 mutations linked to fALS (G93A and A4V) leads to SOD1 intracellular accumulation, which correlates to autophagy dysfunction and microglial activation. In primary contact co-cultures, fALS mutant SOD1 overexpression by microglial cells appears to be neurotoxic by itself. Treatment with the autophagy-inducer trehalose reduced mutant SOD1 accumulation in microglial cells, decreased microglial activation and abrogated neurotoxicity in the co-culture model. These data suggest that i) the alteration of the autophagic pathway due to mutant SOD1 overexpression is involved in microglial activation and neurotoxicity; ii) the induction of autophagy with trehalose reduces microglial SOD1 accumulation through proteasome degradation and activation, leading to neuroprotection. Our results provide a novel contribution towards better understanding key cellular mechanisms in non-cell autonomous ALS neurodegeneration. 相似文献
857.
David B. Doroquez Ilaria Rebay 《Critical reviews in biochemistry and molecular biology》2013,48(6):339-385
ABSTRACTMetazoan development relies on a highly regulated network of interactions between conserved signal transduction pathways to coordinate all aspects of cell fate specification, differentiation, and growth. In this review, we discuss the intricate interplay between the epidermal growth factor receptor (EGFR; Drosophila EGFR/DER) and the Notch signaling pathways as a paradigm for signal integration during development. First, we describe the current state of understanding of the molecular architecture of the EGFR and Notch signaling pathways that has resulted from synergistic studies in vertebrate, invertebrate, and cultured cell model systems. Then, focusing specifically on the Drosophila eye, we discuss how cooperative, sequential, and antagonistic relationships between these pathways mediate the spatially and temporally regulated processes that generate this sensory organ. The common themes underlying the coordination of the EGFR and Notch pathways appear to be broadly conserved and should, therefore, be directly applicable to elucidating mechanisms of information integration and signaling specificity in vertebrate systems. 相似文献
858.
He W Huang C Luo G Dal Prà I Feng J Chen W Ma L Wang Y Chen X Tan J Zhang X Armato U Wu J 《Proteomics》2012,12(7):1059-1072
Just as biomarkers specific for diseases, biomarkers indicative of healthy conditions are valuable for the early diagnosis, monitoring, and prognosis of diseases. Our study focused on discovering via proteomics a stable panel of urinary proteins in the human healthy population. Urine samples were collected three times during 4 months from 100 male and 100 female healthy donors and analyzed through four different fractionation techniques (i.e. in-gel, 2D-LC, OFFGEL, and mRP) coupled with HPLC-Chip-MS/MS. Thus, 1641 urinary proteins were identified with a high confidence, among which 70 exhibiting an intergender/day variation <0.25 were selected and matched with the previously published five largest urinary proteomes to get 56 candidate proteins. Next, a panel comprising 18 intact urinary proteins was constructed by comparing the urinary proteomes via SDS-PAGE and 2DE. Finally, such 18 urinary proteins were validated via enzyme-linked immunosorbent assay in eight healthy individuals. Most of these proteins had been related to multiple rather than to single diseases. Therefore, we surmise that this protein set could be used as a biomarker to assess the human health status. Further determinations of the normal fluctuations of the single urinary proteins in this series using samples from large numbers of healthy individuals are required prior to any application in clinical settings. 相似文献
859.
860.