全文获取类型
收费全文 | 88篇 |
免费 | 16篇 |
专业分类
耳鼻咽喉 | 4篇 |
妇产科学 | 2篇 |
基础医学 | 42篇 |
口腔科学 | 2篇 |
临床医学 | 1篇 |
内科学 | 28篇 |
神经病学 | 8篇 |
外科学 | 1篇 |
综合类 | 2篇 |
预防医学 | 4篇 |
眼科学 | 1篇 |
药学 | 1篇 |
中国医学 | 1篇 |
肿瘤学 | 7篇 |
出版年
2023年 | 1篇 |
2022年 | 1篇 |
2021年 | 1篇 |
2019年 | 2篇 |
2018年 | 1篇 |
2017年 | 1篇 |
2016年 | 1篇 |
2012年 | 2篇 |
2011年 | 5篇 |
2010年 | 3篇 |
2009年 | 3篇 |
2008年 | 8篇 |
2006年 | 5篇 |
2005年 | 6篇 |
2004年 | 8篇 |
2003年 | 4篇 |
2002年 | 3篇 |
2001年 | 1篇 |
2000年 | 11篇 |
1999年 | 4篇 |
1998年 | 1篇 |
1997年 | 5篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1993年 | 2篇 |
1992年 | 4篇 |
1991年 | 4篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1985年 | 3篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1979年 | 1篇 |
1972年 | 1篇 |
排序方式: 共有104条查询结果,搜索用时 15 毫秒
41.
A Falini V Silani A Pizzuti E I Rugarli D Mariani R Bassani A Vegeto F E Baralle G Scarlato 《Functional neurology》1991,6(3):259-261
Adrenal gland involvement in Parkinson's disease was reported by different authors. Further studies became relevant after adrenal was proposed as dopaminergic donor for neurotransplantation. Chromaffin cells were grown in culture and the effects of nerve growth factor (NGF) tested: no differences were observed between parkinsonian and control cells. The expression of the beta-NGF mRNA in the parkinsonian adrenal was analyzed: a specific cDNA was synthesized and a 168 bp portion amplified using PCR. The products were identified and the identity of the fragment was confirmed by sequencing. Quantitative PCR demonstrated a beta-NGF mRNA concentration exceeding 5 fg/micrograms of total adrenal RNA. These findings demonstrate the retained functional capacity of the parkinsonian adrenal to respond to NGF and express the beta-NGF mRNA. 相似文献
42.
43.
Pagani F Raponi M Baralle FE 《Proceedings of the National Academy of Sciences of the United States of America》2005,102(18):6368-6372
It is well established that exonic sequences contain regulatory elements of splicing that overlap with coding capacity. However, the conflict between ensuring splicing efficiency and preserving the coding capacity for an optimal protein during evolution has not been specifically analyzed. In fact, studies on genomic variability in fields as diverse as clinical genetics and molecular evolution mainly focus on the effect of mutations on protein function. Synonymous variations, in particular, are assumed to be functionally neutral both in clinical diagnosis and when measuring evolutionary distances between species. Using the cystic fibrosis transmembrane conductance regulator (CFTR) exon 12 splicing as a model, we have established that about one quarter of synonymous variations result in exon skipping and, hence, in an inactive CFTR protein. Furthermore, comparative splicing evaluation of mammalian sequence divergences showed that artificial combinations of CFTR exon 12 synonymous and nonsynonymous substitutions are incompatible with normal RNA processing. In particular, the combination of the mouse synonymous with the human missense variations causes exon skipping. It follows that there are two sequential levels at which evolutionary selection of genomic variants take place: splicing control and protein function optimization. 相似文献
44.
45.
Improved reactivity of hepatitis C virus core protein epitopes in a conformational antigen-presenting system.
下载免费PDF全文
![点击此处可从《Clinical and Vaccine Immunology : CVI》网站下载免费的PDF全文](/ch/ext_images/free.gif)
E Buratti M Di Michele P Song C Monti-Bragadin E A Scodeller F E Baralle S G Tisminetzky 《Clinical and Vaccine Immunology : CVI》1997,4(2):117-121
Recent studies have identified several epitopes in the N-terminal portion of the nucleocapsid protein which are predominantly recognized by sera of patients infected with hepatitis C virus (HCV). The characterization of the sequences recognized by theses antibodies and the evaluation of their reactivities have been performed mainly with synthetic peptides. However, synthetic peptides are notoriously unreliable as antigens when the immune response is directed against conformational epitopes. In order to improve the detection of antibody responses in HCV-infected patients, we have evaluated the reactivities of three immunodominant regions of the HCV core protein (residues 1 to 20, 21 to 40, and 32 to 46) displayed in a conformation-specific manner on the surface of the Flock House virus (FHV) capsid protein. The results obtained with these proteins in the analysis of 94 serum samples positive by anti-HCV enzyme-linked immunosorbent assay where then compared with those obtained with the corresponding synthetic peptides. The sequence most reactive both with the peptide and with the FHV protein was the region from residues 1 to 20, confirming the low conformational requirements for the display of these residues. On the other hand, the already reported conformational nature of residues 32 to 46 is in keeping with its observed high reactivity when displayed by the FHV recombinant protein and with the low reactivity displayed by its corresponding synthetic peptide. Finally, the high reactivity observed for the chimeric protein displaying the region from residues 21 to 40, as opposed to the results obtained with the synthetic peptide, also suggests that this sequence contains one or more conformational epitopes whose structures cannot be mimicked correctly with synthetic peptides. 相似文献
46.
A female patient of normal intelligence with short stature and Madelung deformity is reported with Léri-Weill dyschondrosteosis and a de novo pseudodicentric X;Y translocation chromosome. The phenotype is consistent with the observed deletion of the SHOX gene by FISH and molecular studies. The Y chromosome breakpoint was in the short arm but proximal to SRY, consistent with her phenotypic sex. X-inactivation studies have shown a skewed pattern in favour of the dic (X;Y) chromosome. The ARSE gene was also deleted on the dic (X;Y) chromosome but chondrodysplasia punctata was not expressed, as CDP is recessive and ARSE escapes inactivation on the normal X chromosome. Breakpoint mapping assisted in karyotype/phenotype correlation and reproductive counselling. In particular, molecular analysis showed that the putative MRX 49 gene for mental retardation is unlikely to be deleted in this case. 相似文献
47.
48.
Expression of lysosomal acid lipase mutants detected in three patients with cholesteryl ester storage disease 总被引:1,自引:0,他引:1
Pagani F; Garcia R; Pariyarath R; Stuani C; Gridelli B; Paone G; Baralle FE 《Human molecular genetics》1996,5(10):1611-1617
Lysosomal acid lipase (LAL) gene mutations were identified in three
patients with cholesteryl ester storage disease (CESD). Direct sequencing
of genomic DNA revealed that: patient 1 was a compound heterozygote for a
P181L mutation and an A to G3' splice site substitution that causes
skipping of exon 7, with a loss of 49 amino acids from LAL (delta 205-253);
patient 2 was a compound heterozygote for a G66V mutation and a 5' splice
site mutation (G to A) that leads to skipping of exon 8 (delta 254-277);
and patient 3 was a compound heterozygote for a L273S mutation and an
unidentified null allele. Furthermore, patients 2 and 3 showed a novel G-2A
polymorphism that could be detected by an Xbal restriction fragment length
polymorphism. All these mutants and a previously reported H274Y allele were
expressed in vitro in HeLa cells using the vaccinia T7 expression system.
The resulting recombinant proteins were inactive towards cholesteryl oleate
and trioleylglycerol, demonstrating the direct involvement of these
mutations in the pathogenesis of CESD. Immunoblotting of normal LAL
expressed in HeLa cells revealed four major molecular forms, at least two
of high molecular mass (54 and 50-51 kDa) and two of low molecular mass (42
and 43 kDa). L273S and P181L substitutions and delta 254-277 were shown to
result in altered LAL molecular forms, some of which suggest that
post-translational processing may interfere with the catalytic activity of
LAL.
相似文献
49.
50.