全文获取类型
收费全文 | 245篇 |
免费 | 20篇 |
国内免费 | 27篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 19篇 |
妇产科学 | 3篇 |
基础医学 | 30篇 |
口腔科学 | 18篇 |
临床医学 | 45篇 |
内科学 | 62篇 |
皮肤病学 | 8篇 |
神经病学 | 3篇 |
特种医学 | 25篇 |
外科学 | 20篇 |
综合类 | 18篇 |
预防医学 | 7篇 |
药学 | 17篇 |
中国医学 | 1篇 |
肿瘤学 | 15篇 |
出版年
2022年 | 2篇 |
2021年 | 1篇 |
2020年 | 1篇 |
2019年 | 3篇 |
2018年 | 5篇 |
2017年 | 6篇 |
2016年 | 7篇 |
2015年 | 5篇 |
2014年 | 6篇 |
2013年 | 12篇 |
2012年 | 4篇 |
2011年 | 5篇 |
2010年 | 11篇 |
2009年 | 10篇 |
2008年 | 5篇 |
2007年 | 11篇 |
2006年 | 7篇 |
2005年 | 14篇 |
2004年 | 4篇 |
2003年 | 1篇 |
2002年 | 7篇 |
2001年 | 9篇 |
2000年 | 4篇 |
1999年 | 8篇 |
1998年 | 21篇 |
1997年 | 18篇 |
1996年 | 17篇 |
1995年 | 13篇 |
1994年 | 14篇 |
1993年 | 3篇 |
1992年 | 3篇 |
1991年 | 3篇 |
1990年 | 3篇 |
1989年 | 7篇 |
1988年 | 5篇 |
1987年 | 5篇 |
1986年 | 10篇 |
1985年 | 4篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1978年 | 3篇 |
1977年 | 3篇 |
1976年 | 4篇 |
1975年 | 3篇 |
排序方式: 共有292条查询结果,搜索用时 15 毫秒
1.
2.
3.
4.
doublecortin is the major gene causing X-linked subcortical laminar heterotopia (SCLH) 总被引:12,自引:0,他引:12
des Portes V; Francis F; Pinard JM; Desguerre I; Moutard ML; Snoeck I; Meiners LC; Capron F; Cusmai R; Ricci S; Motte J; Echenne B; Ponsot G; Dulac O; Chelly J; Beldjord C 《Human molecular genetics》1998,7(7):1063-1070
Subcortical laminar heterotopia (SCLH), or 'double cortex', is a cortical
dysgenesis disorder associated with a defect in neuronal migration.
Clinical manifestations are epilepsy and mental retardation. This disorder,
which mainly affects females, can be inherited in a single pedigree with
lissencephaly, a more severe disease which affects the male individuals.
This clinical entity has been described as X- SCLH/LIS syndrome. Recently
we have demonstrated that the doublecortin gene, which is localized on the
X chromosome, is implicated in this disorder. We have now performed a
systematic mutation analysis of doublecortin in 11 unrelated females with
SCLH (one familial and 10 sporadic cases) and have identified mutations in
10/11 cases. The sequence differences include nonsense, splice site and
missense mutations and these were found throughout the gene. These results
provide strong evidence that loss of function of doublecortin is the major
cause of SCLH. The absence of phenotype-genotype correlations suggests that
X-inactivation patterns of neuronal precursor cells are likely to
contribute to the variable clinical severity of this disorder in females.
相似文献
5.
6.
Stein TP; Oram-Smith JC; Leskiw MJ; Wallace HW; Long LC; Leonard JM 《The American journal of physiology》1976,230(5):1321-1325
7.
Incomplete rescue of cystic fibrosis transmembrane conductance regulator deficient mice by the human CFTR cDNA 总被引:2,自引:2,他引:2
Rozmahel R; Gyomorey K; Plyte S; Nguyen V; Wilschanski M; Durie P; Bear CE; Tsui LC 《Human molecular genetics》1997,6(7):1153-1162
We have used a mouse model to study the ability of human CFTR to correct
the defect in mice deficient of the endogenous protein. In this model,
expression of the endogenous Cftr gene was disrupted and replaced with a
human CFTR cDNA by a gene targeted 'knock-in' event. Animals homozygous for
the gene replacement failed to show neither improved intestinal pathology
nor survival when compared to mice completely lacking CFTR. RNA analyses
showed that the human CFTR sequence was transcribed from the targeted
allele in the respiratory and intestinal epithelial cells. Furthermore, in
vivo potential difference measurements showed that basal CFTR chloride
channel activity was present in the apical membranes of both nasal and
rectal epithelial cells in all homozygous knock-in animals examined. Ussing
chamber studies showed, however, that the cAMP-mediated chloride channel
function was impaired in the intestinal tract among the majority of
homozygous knock-in animals. Hence, failure to correct the intestinal
pathology associated with loss of endogenous CFTR was related to
inefficient functional expression of the human protein in mice. These
results emphasize the need to understand the tissue- specific expression
and regulation of CFTR function when animal models are used in gene therapy
studies.
相似文献
8.
Successful outcome with day 4 embryo transfer after preimplantation diagnosis for genetically transmitted diseases 总被引:4,自引:5,他引:4
Preimplantation genetic diagnosis was performed in 61 day 3 embryos
obtained by in-vitro fertilization from seven patient carriers of
haemophilia, Marfan's syndrome, Bloch-Sulzemberg syndrome (incontinentia
pigmentosa) or X chromosome-linked immune deficiency, retinitis pigmentosa,
and FG syndrome, which is characterized by mental retardation and
hypotonia. After multiplex polymerase chain reaction, 16 embryos were
diagnosed as being unaffected, and these were transferred to the uterus on
the following day (day 4). Of these embryos, six (37.5%) implanted,
resulting in the delivery of a singleton and a twin pregnancy, a late
second trimester miscarriage (twins at week 20) and a first trimester
miscarriage at week 8. All the diagnoses were confirmed by amniocentesis.
We report for the first time a late day 4 transfer of biopsied human
embryos undergoing preimplantation genetic diagnosis. This transfer
schedule allows an extra day to perform genetic analyses on single
blastomeres and to monitor any adverse effect of the biopsy procedure.
相似文献
9.
Marjolijn Bornebroek Joost Haan Marion LC Maat-Schieman Sjoerd G Van Duinen Raymund AC Roos 《Brain pathology (Zurich, Switzerland)》1996,6(2):111-114
Hereditary cerebral hemorrhage with amyloidosis - Dutch type (HCHWA-D) is an autosomal dominant disease caused by deposition of β-amyloid in the leptomeningeal arteries and cortical arterioles, in addition to preamyloid deposits and amyloid plaques in the brain parenchyma.
The disease is due to a point mutation at codon 693 of the amyloid precursor protein (βPP) gene at chromosome 21. Since this point mutation is diagnostic for HCHWA-D, presymptomatic testing is feasible and offered, together with genetic counselling and psychological support, to subjects at risk. HCHWA-D is clinically characterized by recurrent strokes, in addition to dementia, which can occur after the first stroke but also preceding it. Radiological studies revealed focal lesions (hemorrhages, hemorrhagic and non-hemorrhagic infarctions) and diffuse white matter damage. Diffuse white matter hyperintensities on MRI are an early symptom of HCHWA-D since they have been found on MRI scans of subjects who had not suffered a stroke.
The presence of the diagnostic point mutation makes HCHWA-D a useful model to study the effects of cerebral amyloid angiopathy in vivo. The characteristic pathological abnormalities and its implications for Alzheimer's disease will be discussed in Part II of this article 相似文献
The disease is due to a point mutation at codon 693 of the amyloid precursor protein (βPP) gene at chromosome 21. Since this point mutation is diagnostic for HCHWA-D, presymptomatic testing is feasible and offered, together with genetic counselling and psychological support, to subjects at risk. HCHWA-D is clinically characterized by recurrent strokes, in addition to dementia, which can occur after the first stroke but also preceding it. Radiological studies revealed focal lesions (hemorrhages, hemorrhagic and non-hemorrhagic infarctions) and diffuse white matter damage. Diffuse white matter hyperintensities on MRI are an early symptom of HCHWA-D since they have been found on MRI scans of subjects who had not suffered a stroke.
The presence of the diagnostic point mutation makes HCHWA-D a useful model to study the effects of cerebral amyloid angiopathy in vivo. The characteristic pathological abnormalities and its implications for Alzheimer's disease will be discussed in Part II of this article 相似文献
10.
同种异体黑素细胞移植治疗白癜风 总被引:2,自引:2,他引:0
0 引言 白癜风患者免疫紊乱 ,黑素细胞 (melanocyte,MC)异体移植有可能不被排斥 ,治疗如成功将有很大临床前景 [1 ] .探索同种异体黑素细胞移植后的效果很有意义 .1 病例报告 女 ,2 7岁 ,确诊白癜风 (稳定期 ) ,患者皮肤自幼出现色素脱失斑 ,逐渐增多扩大 . 1996年外用“敏白灵”,前2 mo有效 . 1999- 0 7外用补骨酯酊 ,日服 5 g· L- 1 硫酸铜 10m L和中药 1剂 ,转移因子 4m L ,sc,1· 2 d- 1 .皮损缩小 ,4mo后稳定 .用健康男青年环切的包皮培养 MC,第 4代大约80 %融合时 ,用 2 .5 g· L- 1 胰酶消化 5 min,加入含 2 0 0 g·L- 1小… 相似文献