全文获取类型
收费全文 | 1202篇 |
免费 | 70篇 |
国内免费 | 9篇 |
专业分类
1281篇 |
出版年
2023年 | 28篇 |
2022年 | 40篇 |
2021年 | 53篇 |
2020年 | 43篇 |
2019年 | 66篇 |
2018年 | 62篇 |
2017年 | 32篇 |
2016年 | 40篇 |
2015年 | 56篇 |
2014年 | 72篇 |
2013年 | 100篇 |
2012年 | 59篇 |
2011年 | 74篇 |
2010年 | 65篇 |
2009年 | 45篇 |
2008年 | 52篇 |
2007年 | 61篇 |
2006年 | 52篇 |
2005年 | 30篇 |
2004年 | 44篇 |
2003年 | 31篇 |
2002年 | 29篇 |
2001年 | 13篇 |
2000年 | 20篇 |
1999年 | 14篇 |
1998年 | 19篇 |
1997年 | 18篇 |
1996年 | 8篇 |
1995年 | 8篇 |
1994年 | 7篇 |
1993年 | 6篇 |
1992年 | 5篇 |
1991年 | 2篇 |
1989年 | 3篇 |
1988年 | 3篇 |
1987年 | 1篇 |
1986年 | 5篇 |
1985年 | 3篇 |
1984年 | 5篇 |
1982年 | 5篇 |
1980年 | 2篇 |
排序方式: 共有1281条查询结果,搜索用时 15 毫秒
101.
Kevin Boylan Cui Yang† Julia Crook‡ Karen Overstreet Michael Heckman‡ Yong Wang§ David Borchelt† Gerry Shaw†§ 《Journal of neurochemistry》2009,111(5):1182-1191
Levels of neurofilament subunits, potential biomarkers of motor axon breakdown, are increased in amyotrophic lateral sclerosis (ALS) patient's CSF but data on blood are not available. We measured blood levels of the phosphorylated axonal form of neurofilament H (pNF-H) by ELISA in transgenic rodent models of superoxide dismutase 1 (SOD1) ALS, and in 20 ALS patients and 20 similar aged controls monthly for 4 months. All symptomatic rodent ALS models showed robust levels of blood pNF-H, while control rodents or mice transgenic for unmutated SOD1 showed no detectable blood pNF-H. Average pNF-H levels in the G93A SOD1 mouse progressively increased from day 74 through death (day ∼130). Median blood pNF-H level in ALS patients was 2.8-fold higher than controls ( p < 0.001). Median ALSFRS-R declined a median of 0.8 pt/month ( p < 0.001); higher baseline pNF-H level appeared to be associated with faster ALSFRS-R decline over 4 months ( p = 0.087). The median rate of decline in ALSFRS-R was 1.9 pt/month in patients with baseline pNF-H levels above the median pNF-H value of 0.53 ng/mL; ALSFRS-R declined at a median of 0.6 pt/month in patients below this level. The pNF-H levels were relatively stable month to month in individual patients, raising questions regarding the molecular pathogenesis of ALS. Baseline control human pNF-H levels were higher in men than women and increased minimally over time. These data suggest that blood pNF-H can be used to monitor axonal degeneration in ALS model rodents and support further study of this protein as a potential biomarker of disease prognosis in ALS patients. 相似文献
102.
103.
《Molecular & cellular proteomics : MCP》2022,21(11):100422
Cellular biomolecular complexes including protein–protein, protein–RNA, and protein–DNA interactions regulate and execute most biological functions. In particular in brain, protein–protein interactions (PPIs) mediate or regulate virtually all nerve cell functions, such as neurotransmission, cell–cell communication, neurogenesis, synaptogenesis, and synaptic plasticity. Perturbations of PPIs in specific subsets of neurons and glia are thought to underly a majority of neurobiological disorders. Therefore, understanding biological functions at a cellular level requires a reasonably complete catalog of all physical interactions between proteins. An enzyme-catalyzed method to biotinylate proximal interacting proteins within 10 to 300 nm of each other is being increasingly used to characterize the spatiotemporal features of complex PPIs in brain. Thus, proximity labeling has emerged recently as a powerful tool to identify proteomes in distinct cell types in brain as well as proteomes and PPIs in structures difficult to isolate, such as the synaptic cleft, axonal projections, or astrocyte–neuron junctions. In this review, we summarize recent advances in proximity labeling methods and their application to neurobiology. 相似文献
104.
《Cell》2021,184(16):4168-4185.e21
105.
Calcium (Ca) concentrations were studied in the central nervous system (CNS) of four patients with definite multiple sclerosis
(MS, average age 49 yr) and five controls (average age 68 yr). The Ca concentration was determined by neutron activation analysis
in autopsy samples taken from the 26 subanatomical regions of CNS tissues. Although the mean Ca concentration in the 26 CNS
regions combined was higher in the four MS patients than in the controls, the content of white matter was lower. Whether or
not this significantly lower Ca concentration found in the white matter of MS patients plays an important role in the demyelinating
process remains unclear, although that lower concentration seems not be age dependent, but MS specific. 相似文献
106.
Rebeca Busto Jorge Serna Aránzazu Perianes-Cachero Rocío Quintana-Portillo David García-Seisdedos Alberto Canfrán-Duque Carlos L. Paino Milagros Lerma María E. Casado Antonia Martín-Hidalgo Eduardo Arilla-Ferreiro Miguel A. Lasunción Óscar Pastor 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2018,1863(9):958-967
Experimental autoimmune encephalomyelitis (EAE), the most common model for multiple sclerosis, is characterized by inflammatory cell infiltration into the central nervous system and demyelination. Previous studies have demonstrated that administration of some polyphenols may reduce the neurological alterations of EAE. In this work, we show that ellagic acid, a polyphenolic compound, is beneficial in EAE, most likely through stimulation of ceramide biosynthesis within the brain. EAE was induced in Lewis rats by injection of guinea-pig spinal cord tissue along with Freund's complete adjuvant containing Mycobacterium tuberculosis. Clinical signs first appeared at day 8 post-immunization and reached a peak within 3?days, coincident with reduction of myelin basic protein (MBP) in the cortex. Sphingolipids, the other major components of myelin, also decreased at the acute phase of EAE, both in the cerebral cortex and in the spinal cord. In rats receiving ellagic acid in the drinking water from 2?days before immunization, the onset of the disease was delayed and clinical signs were reduced. This amelioration of clinical signs was accompanied by sustained levels of both MBP and sphingolipid in the cortex, without apparent changes in infiltration of inflammatory CD3+ T-cells, microglial activation, or weight loss, which together suggest a neuroprotective effect of ellagic acid. Finally, in glioma and oligodendroglioma cells we demonstrate that urolithins, the ellagic acid metabolites that circulate in plasma, stimulate the synthesis of ceramide. Together these data suggest that ellagic acid consumption protects against demyelination in rats with induced EAE, likely by a mechanism involving sphingolipid synthesis. 相似文献
107.
108.
109.
110.
Ralf M. Luche Robert Maiwald Elaine J. Carlson Charles J. Epstein 《Molecular and cellular biochemistry》1997,168(1-2):191-194
All mutations in the human gene for CuZn superoxide dismutase (CuZnSOD) reported to date are associated with the disease amyotrophic lateral sclerosis (ALS). These mutations, mostly of a familial nature (ALS 1, MIM 105400), span all of the coding region of this enzyme except for a highly conserved centrally located domain that includes all of exon III. We describe the identification and characterization of two mutations in this region, both found in mice. One mutation, a glutamate to lysine amino acid substitution was found in position 77 (E77K) of the strain SOD1/Ei distributed by the Jackson Laboratory. The other mutation, a lysine to glutamate substitution at position 70 (K70E) of a human transgene, was discovered in mouse line TgHS/SF-155. Enzyme activity measurements and heterodimer analysis of the CuZn SOD variant in SOD1/Ei suggest a mild loss of activity, which differs from the enzyme activity losses detected in patients with autosomal dominant ALS 1. Similarly, the presence of the mutant transgene in TgHS/SF 155 does not produce any phenotypic manifestations. 相似文献