全文获取类型
收费全文 | 111篇 |
免费 | 0篇 |
专业分类
现状及发展 | 3篇 |
研究方法 | 4篇 |
综合类 | 104篇 |
出版年
2012年 | 2篇 |
2011年 | 2篇 |
2008年 | 3篇 |
2007年 | 4篇 |
2006年 | 1篇 |
2004年 | 3篇 |
2003年 | 2篇 |
2002年 | 5篇 |
2001年 | 11篇 |
2000年 | 25篇 |
1999年 | 3篇 |
1994年 | 1篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 4篇 |
1989年 | 1篇 |
1986年 | 1篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 5篇 |
1981年 | 9篇 |
1980年 | 3篇 |
1979年 | 9篇 |
1978年 | 5篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 3篇 |
1970年 | 1篇 |
1967年 | 2篇 |
排序方式: 共有111条查询结果,搜索用时 31 毫秒
61.
Schmutz J Wheeler J Grimwood J Dickson M Yang J Caoile C Bajorek E Black S Chan YM Denys M Escobar J Flowers D Fotopulos D Garcia C Gomez M Gonzales E Haydu L Lopez F Ramirez L Retterer J Rodriguez A Rogers S Salazar A Tsai M Myers RM 《Nature》2004,429(6990):365-368
As the final sequencing of the human genome has now been completed, we present the results of the largest examination of the quality of the finished DNA sequence. The completed study covers the major contributing sequencing centres and is based on a rigorous combination of laboratory experiments and computational analysis. 相似文献
62.
Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein 总被引:29,自引:0,他引:29
Lewis J McGowan E Rockwood J Melrose H Nacharaju P Van Slegtenhorst M Gwinn-Hardy K Paul Murphy M Baker M Yu X Duff K Hardy J Corral A Lin WL Yen SH Dickson DW Davies P Hutton M 《Nature genetics》2000,25(4):402-405
Neurofibrillary tangles (NFT) composed of the microtubule-associated protein tau are prominent in Alzheimer disease (AD), Pick disease, progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Mutations in the gene (Mtapt) encoding tau protein cause frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), thereby proving that tau dysfunction can directly result in neurodegeneration. Expression of human tau containing the most common FTDP-17 mutation (P301L) results in motor and behavioural deficits in transgenic mice, with age- and gene-dose-dependent development of NFT. This phenotype occurred as early as 6.5 months in hemizygous and 4.5 months in homozygous animals. NFT and Pick-body-like neuronal lesions occurred in the amygdala, septal nuclei, pre-optic nuclei, hypothalamus, midbrain, pons, medulla, deep cerebellar nuclei and spinal cord, with tau-immunoreactive pre-tangles in the cortex, hippocampus and basal ganglia. Areas with the most NFT had reactive gliosis. Spinal cord had axonal spheroids, anterior horn cell loss and axonal degeneration in anterior spinal roots. We also saw peripheral neuropathy and skeletal muscle with neurogenic atrophy. Brain and spinal cord contained insoluble tau that co-migrated with insoluble tau from AD and FTDP-17 brains. The phenotype of mice expressing P301L mutant tau mimics features of human tauopathies and provides a model for investigating the pathogenesis of diseases with NFT. 相似文献
63.
64.
65.
66.
67.
68.
Neurons are thought to use diverse families of cell-surface molecules for cell recognition during circuit assembly. In Drosophila, alternative splicing of the Down syndrome cell adhesion molecule (Dscam) gene potentially generates 38,016 closely related transmembrane proteins of the immunoglobulin superfamily, each comprising one of 19,008 alternative ectodomains linked to one of two alternative transmembrane segments. These ectodomains show isoform-specific homophilic binding, leading to speculation that Dscam proteins mediate cell recognition. Genetic studies have established that Dscam is required for neural circuit assembly, but the extent to which isoform diversity contributes to this process is not known. Here we provide conclusive evidence that Dscam diversity is essential for circuit assembly. Using homologous recombination, we reduced the entire repertoire of Dscam ectodomains to just a single isoform. Neural circuits in these mutants are severely disorganized. Furthermore, we show that it is crucial for neighbouring neurons to express distinct isoforms, but that the specific identity of the isoforms expressed in an individual neuron is unimportant. We conclude that Dscam diversity provides each neuron with a unique identity by which it can distinguish its own processes from those of other neurons, and that this self-recognition is essential for wiring the Drosophila brain. 相似文献
69.
70.