全文获取类型
收费全文 | 1057篇 |
免费 | 86篇 |
出版年
2024年 | 2篇 |
2023年 | 5篇 |
2022年 | 6篇 |
2021年 | 24篇 |
2020年 | 7篇 |
2019年 | 9篇 |
2018年 | 27篇 |
2017年 | 33篇 |
2016年 | 39篇 |
2015年 | 65篇 |
2014年 | 49篇 |
2013年 | 78篇 |
2012年 | 82篇 |
2011年 | 72篇 |
2010年 | 58篇 |
2009年 | 50篇 |
2008年 | 83篇 |
2007年 | 81篇 |
2006年 | 63篇 |
2005年 | 64篇 |
2004年 | 59篇 |
2003年 | 50篇 |
2002年 | 51篇 |
2001年 | 8篇 |
2000年 | 7篇 |
1999年 | 7篇 |
1998年 | 6篇 |
1997年 | 4篇 |
1996年 | 8篇 |
1995年 | 5篇 |
1994年 | 11篇 |
1993年 | 3篇 |
1992年 | 1篇 |
1991年 | 3篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1988年 | 5篇 |
1987年 | 3篇 |
1986年 | 1篇 |
1985年 | 5篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1977年 | 1篇 |
1974年 | 1篇 |
1968年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有1143条查询结果,搜索用时 281 毫秒
171.
Emanuela Mhillaj Stefania Catino Fiorella M. Miceli Rosaria Santangelo Luigia Trabace Vincenzo Cuomo Cesare Mancuso 《Molecular neurobiology》2018,55(2):905-916
Over the last years, many studies reported on the antioxidant effects of ferulic acid (FA) in preclinical models of dementia through the activation of the heme oxygenase/biliverdin reductase (HO/BVR) system. However, only a few studies evaluated whether FA could improve neurological function under milder conditions, such as psychological stress. The aim of this study was to investigate the effects of FA (150 mg/kg intraperitoneal route) on cognitive function in male Wistar rats exposed to emotional arousal. Animals were randomly assigned to two experimental groups, namely not habituated or habituated to the experimental context, and the novel object recognition test was used to evaluate their cognitive performance. The administration of FA significantly increased long-term retention memory in not habituated rats. Ferulic acid increased the expression of HO-1 in the hippocampus and frontal cortex of not habituated rats only, whereas HO-2 resulted differently modulated in these cognitive brain areas. No significant effects on either HO-1 or HO-2 or BVR were observed in the cerebellum of both habituated and not habituated rats. Ferulic acid activated the stress axis in not habituated rats, as shown by the increase in hypothalamic corticotrophin-releasing hormone levels. Pre-treatment with Sn-protoporphyrin-IX [0.25 μmol/kg, intracerebroventricular route (i.c.v.)], a well-known inhibitor of HO activity through which carbon monoxide (CO) and biliverdin (BV) are generated, abolished the FA-induced improvement of cognitive performance only in not habituated rats, suggesting a role for HO-derived by-products. The CO-donor tricarbonyldichlororuthenium (II) (30 nmol/kg i.c.v.) mimicked the FA-related improvement of cognitive skills only in not habituated rats, whereas BV did not have any effect in any group. In conclusion, these results set the stage for subsequent studies on the neuropharmacological action of FA under conditions of psychological stress. 相似文献
172.
Irene Zubiri Vittoria Lombardi Michael Bremang Vikram Mitra Giovanni Nardo Rocco Adiutori Ching-Hua Lu Emanuela Leoni Ping Yip Ozlem Yildiz Malcolm Ward Linda Greensmith Caterina Bendotti Ian Pike Andrea Malaspina 《Molecular neurodegeneration》2018,13(1):60
Background
It is unclear to what extent pre-clinical studies in genetically homogeneous animal models of amyotrophic lateral sclerosis (ALS), an invariably fatal neurodegenerative disorder, can be informative of human pathology. The disease modifying effects in animal models of most therapeutic compounds have not been reproduced in patients. To advance therapeutics in ALS, we need easily accessible disease biomarkers which can discriminate across the phenotypic variants observed in ALS patients and can bridge animal and human pathology. Peripheral blood mononuclear cells alterations reflect the rate of progression of the disease representing an ideal biological substrate for biomarkers discovery.Methods
We have applied TMTcalibrator?, a novel tissue-enhanced bio fluid mass spectrometry technique, to study the plasma proteome in ALS, using peripheral blood mononuclear cells as tissue calibrator. We have tested slow and fast progressing SOD1G93A mouse models of ALS at a pre-symptomatic and symptomatic stage in parallel with fast and slow progressing ALS patients at an early and late stage of the disease. Immunoassays were used to retest the expression of relevant protein candidates.Results
The biological features differentiating fast from slow progressing mouse model plasma proteomes were different from those identified in human pathology, with only processes encompassing membrane trafficking with translocation of GLUT4, innate immunity, acute phase response and cytoskeleton organization showing enrichment in both species. Biological processes associated with senescence, RNA processing, cell stress and metabolism, major histocompatibility complex-II linked immune-reactivity and apoptosis (early stage) were enriched specifically in fast progressing ALS patients. Immunodetection confirmed regulation of the immunosenescence markers Galectin-3, Integrin beta 3 and Transforming growth factor beta-1 in plasma from pre-symptomatic and symptomatic transgenic animals while Apolipoprotein E differential plasma expression provided a good separation between fast and slow progressing ALS patients.Conclusions
These findings implicate immunosenescence and metabolism as novel targets for biomarkers and therapeutic discovery and suggest immunomodulation as an early intervention. The variance observed in the plasma proteomes may depend on different biological patterns of disease progression in human and animal model.173.
Vanessa Capone Emanuela Clemente Elena Restelli Antonella Di Campli Samantha Sperduti Francesca Ornaghi Laura Pietrangelo Feliciano Protasi Roberto Chiesa Michele Sallese 《生物化学与生物物理学报:疾病的分子基础》2018,1864(10):3164-3180
Loss-of-function mutations in the SIL1 gene are linked to Marinesco-Sjögren syndrome (MSS), a rare multisystem disease of infancy characterized by cerebellar and skeletal muscle degeneration. SIL1 is a ubiquitous adenine nucleotide exchange factor for the endoplasmic reticulum (ER) chaperone BiP. The complexity of mechanisms by which loss of SIL1 causes MSS is not yet fully understood. We used HeLa cells to test the hypothesis that impaired protein folding in the ER due to loss of SIL1 could affect secretory trafficking, impairing the transport of cargoes essential for the function of MSS vulnerable cells. Immunofluorescence and ultrastructural analysis of SIL1-knocked-down cells detected ER chaperone aggregation, enlargement of the Golgi complex, increased autophagic vacuoles, and mitochondrial swelling. SIL1-interefered cells also had delayed ER-to-plasma membrane transport with retention of Na+/K+-ATPase and procollagen-I in the ER and Golgi, and increased apoptosis. The PERK pathway of the unfolded protein response was activated in SIL1-interfered cells, and the PERK inhibitor GSK2606414 attenuated the morphological and functional alterations of the secretory pathway, and significantly reduced cell death. These results indicate that loss of SIL1 is associated with alterations of secretory transport, and suggest that inhibiting PERK signalling may alleviate the cellular pathology of SIL1-related MSS. 相似文献
174.
Leishmaniasis encompasses a number of disease syndromes, caused by several species of the digenetic protozoan Leishmania, and is transmitted by sandflies. The mouse model of the disease has been used to identify genes involved in disease susceptibility--for example, the Slc11a1 gene, important in resistance to Leishmania donovani--and to map loci important in Leishmania major infection. The genetics of the host response to L. major has been shown to be complex and to involve much more than the T helper cell response. 相似文献
175.
A comparative analysis of microscopic alterations in modern and ancient undecalcified and decalcified dry bones
下载免费PDF全文
![点击此处可从《American journal of physical anthropology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
176.
177.
Serum From Advanced Heart Failure Patients Promotes Angiogenic Sprouting and Affects the Notch Pathway in Human Endothelial Cells
下载免费PDF全文
![点击此处可从《Journal of cellular physiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Micaela Pannella Cristiana Caliceti Francesca Fortini Giorgio Aquila Francesco Vieceli Dalla Sega Antonio Pannuti Cinzia Fortini Marco Bruno Morelli Alessandro Fucili Gloria Francolini Rebecca Voltan Paola Secchiero Giovanni Dinelli Emanuela Leoncini Manuela Ferracin Silvana Hrelia Lucio Miele Paola Rizzo 《Journal of cellular physiology》2016,231(12):2700-2710
178.
Genetic and Functional Analysis of Polymorphisms in the Human Dopamine Receptor and Transporter Genes in Small Cell Lung Cancer
下载免费PDF全文
![点击此处可从《Journal of cellular physiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
179.