全文获取类型
收费全文 | 2287篇 |
免费 | 171篇 |
出版年
2024年 | 3篇 |
2023年 | 10篇 |
2022年 | 33篇 |
2021年 | 59篇 |
2020年 | 31篇 |
2019年 | 53篇 |
2018年 | 78篇 |
2017年 | 52篇 |
2016年 | 92篇 |
2015年 | 117篇 |
2014年 | 156篇 |
2013年 | 169篇 |
2012年 | 222篇 |
2011年 | 213篇 |
2010年 | 141篇 |
2009年 | 99篇 |
2008年 | 152篇 |
2007年 | 150篇 |
2006年 | 114篇 |
2005年 | 111篇 |
2004年 | 107篇 |
2003年 | 75篇 |
2002年 | 67篇 |
2001年 | 7篇 |
2000年 | 9篇 |
1999年 | 18篇 |
1998年 | 18篇 |
1997年 | 17篇 |
1996年 | 11篇 |
1995年 | 9篇 |
1994年 | 6篇 |
1993年 | 10篇 |
1992年 | 7篇 |
1991年 | 5篇 |
1990年 | 5篇 |
1989年 | 4篇 |
1988年 | 6篇 |
1987年 | 2篇 |
1985年 | 4篇 |
1983年 | 2篇 |
1981年 | 6篇 |
1980年 | 2篇 |
1977年 | 2篇 |
1972年 | 2篇 |
1969年 | 1篇 |
1909年 | 1篇 |
排序方式: 共有2458条查询结果,搜索用时 31 毫秒
941.
942.
Elisa Bisicchia Roberta Mastrantonio Annalisa Nobili Claudia Palazzo Livia La Barbera Laura Latini Francesco Millozzi Valeria Sasso Daniela Palacios Marcello DAmelio Maria Teresa Viscomi 《Cell death & disease》2022,13(4)
The pathogenic mechanisms that underlie the progression of remote degeneration after spinal cord injury (SCI) are not fully understood. In this study, we examined the relationship between endoplasmic reticulum (ER) stress and macroautophagy, hereafter autophagy, and its contribution to the secondary damage and outcomes that are associated with remote degeneration after SCI. Using a rat model of spinal cord hemisection at the cervical level, we measured ER stress and autophagy markers in the axotomized neurons of the red nucleus (RN). In SCI animals, mRNA and protein levels of markers of ER stress, such as GRP78, CHOP, and GADD34, increased 1 day after the injury, peaking on Day 5. Notably, in SCI animals, the increase of ER stress markers correlated with a blockade in autophagic flux, as evidenced by the increase in microtubule-associated protein 2 light chain 3 (LC3-II) and p62/SQSTM1 (p62) and the decline in LAMP1 and LAMP2 levels. After injury, treatment with guanabenz protected neurons from UPR failure and increased lysosomes biogenesis, unblocking autophagic flux. These effects correlated with greater activation of TFEB and improved neuronal survival and functional recovery—effects that persisted after suspension of the treatment. Collectively, our results demonstrate that in remote secondary damage, impairments in autophagic flux are intertwined with ER stress, an association that contributes to the apoptotic cell death and functional damage that are observed after SCI.Subject terms: Cell death in the nervous system, Neurodegeneration, Molecular neuroscience 相似文献
943.
944.
945.
946.
Immunological and metabolomic impacts of administration of Cry1Ab protein and MON 810 maize in mouse 总被引:1,自引:0,他引:1
Adel-Patient K Guimaraes VD Paris A Drumare MF Ah-Leung S Lamourette P Nevers MC Canlet C Molina J Bernard H Créminon C Wal JM 《PloS one》2011,6(1):e16346
We have investigated the immunological and metabolomic impacts of Cry1Ab administration to mice, either as a purified protein or as the Cry1Ab-expressing genetically modified (GM) MON810 maize. Humoral and cellular specific immune responses induced in BALB/cJ mice after intra-gastric (i.g.) or intra-peritoneal (i.p.) administration of purified Cry1Ab were analyzed and compared with those induced by proteins of various immunogenic and allergic potencies. Possible unintended effects of the genetic modification on the pattern of expression of maize natural allergens were studied using IgE-immunoblot and sera from maize-allergic patients. Mice were experimentally sensitized (i.g. or i.p. route) with protein extracts from GM or non-GM maize, and then anti-maize proteins and anti-Cry1Ab-induced immune responses were analyzed. In parallel, longitudinal metabolomic studies were performed on the urine of mice treated via the i.g. route. Weak immune responses were observed after i.g. administration of the different proteins. Using the i.p. route, a clear Th2 response was observed with the known allergenic proteins, whereas a mixed Th1/Th2 immune response was observed with immunogenic protein not known to be allergenic and with Cry1Ab. This then reflects protein immunogenicity in the BALB/c Th2-biased mouse strain rather than allergenicity. No difference in natural maize allergen profiles was evidenced between MON810 and its non-GM comparator. Immune responses against maize proteins were quantitatively equivalent in mice treated with MON810 vs the non-GM counterpart and no anti-Cry1Ab-specific immune response was detected in mice that received MON810. Metabolomic studies showed a slight "cultivar" effect, which represented less than 1% of the initial metabolic information. Our results confirm the immunogenicity of purified Cry1Ab without evidence of allergenic potential. Immunological and metabolomic studies revealed slight differences in mouse metabolic profiles after i.g. administration of MON810 vs its non-GM counterpart, but no significant unintended effect of the genetic modification on immune responses was seen. 相似文献
947.
Costantini D Marasco V Møller AP 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2011,181(4):447-456
Prolonged high secretion of glucocorticoids normally reflects a state of chronic stress, which has been associated with an
increase in disease susceptibility and reduction in Darwinian fitness. Here, we hypothesize that an increase in oxidative
stress accounts for the detrimental effects of prolonged high secretion of glucocorticoids. We performed a meta-analysis on
studies where physiological stress was induced by administration of glucocorticoids to evaluate the magnitude of their effects
on oxidative stress. Glucocorticoids have a significant effect on oxidative stress (Pearson r = 0.552), although this effect depends on the duration of treatment, and is larger in long-term experiments. Importantly,
there was a significant effect on tissue, with brain and heart being the most and the least susceptible to GC-induced oxidative
stress, respectively. Furthermore, effect size was larger (1) in studies using both sexes compared to males only, (2) when
corticosterone rather than dexamethasone was administered and (3) in juveniles than in adults. These effects were not confounded
by species, biochemical biomarker, or whether wild or laboratory animals were studied. In conclusion, our meta-analysis suggests
that GC-induced oxidative stress could be a further mechanism underlying increases in disease susceptibility and decreases
in Darwinian fitness observed under chronic stress. 相似文献
948.
Oualid Benkarim Casey Paquola Bo-yong Park Valeria Kebets Seok-Jun Hong Reinder Vos de Wael Shaoshi Zhang B. T. Thomas Yeo Michael Eickenberg Tian Ge Jean-Baptiste Poline Boris C. Bernhardt Danilo Bzdok 《PLoS biology》2022,20(4)
Brain imaging research enjoys increasing adoption of supervised machine learning for single-participant disease classification. Yet, the success of these algorithms likely depends on population diversity, including demographic differences and other factors that may be outside of primary scientific interest. Here, we capitalize on propensity scores as a composite confound index to quantify diversity due to major sources of population variation. We delineate the impact of population heterogeneity on the predictive accuracy and pattern stability in 2 separate clinical cohorts: the Autism Brain Imaging Data Exchange (ABIDE, n = 297) and the Healthy Brain Network (HBN, n = 551). Across various analysis scenarios, our results uncover the extent to which cross-validated prediction performances are interlocked with diversity. The instability of extracted brain patterns attributable to diversity is located preferentially in regions part of the default mode network. Collectively, our findings highlight the limitations of prevailing deconfounding practices in mitigating the full consequences of population diversity.Brain-imaging research enjoys increasing adoption of supervised machine learning for single-subject disease classification. This study explores the contribution of diversity-aware machine learning models to tracking, unpacking and understanding out-of-distribution generalization in large-scale neuroimaging datasets, and shows that population diversity is a key factor contributing to generalization performance. 相似文献
949.
Gabriela V. Levy Carolina P. Ba?uelos Analía G. Níttolo Gastón E. Ortiz Nicolás Mendiondo Georgina Moretti Valeria S. Tekiel Daniel O. Sánchez 《PloS one》2015,10(8)
Arginine-Serine (RS) domain-containing proteins are RNA binding proteins with multiple functions in RNA metabolism. In mammalian cells this group of proteins is also implicated in regulation and coordination of cell cycle and apoptosis. In trypanosomes, an early branching group within the eukaryotic lineage, this group of proteins is represented by 3 members, two of them are SR proteins and have been recently shown to be involved in rRNA processing as well as in pre-mRNA splicing and stability. Here we report our findings on the 3rd member, the SR-related protein TbRRM1. In the present study, we showed that TbRRM1 ablation by RNA-interference in T. brucei procyclic cells leads to cell-cycle block, abnormal cell elongation compatible with the nozzle phenotype and cell death by an apoptosis-like mechanism. Our results expand the role of the trypanosomal RS-domain containing proteins in key cellular processes such as cell cycle and apoptosis-like death, roles also carried out by the mammalian SR proteins, and thus suggesting a conserved function in this phylogenetically conserved protein family. 相似文献
950.