全文获取类型
收费全文 | 271篇 |
免费 | 27篇 |
国内免费 | 4篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 19篇 |
妇产科学 | 9篇 |
基础医学 | 129篇 |
口腔科学 | 2篇 |
临床医学 | 14篇 |
内科学 | 36篇 |
皮肤病学 | 2篇 |
神经病学 | 25篇 |
特种医学 | 1篇 |
外科学 | 9篇 |
综合类 | 9篇 |
预防医学 | 4篇 |
眼科学 | 4篇 |
药学 | 4篇 |
肿瘤学 | 34篇 |
出版年
2023年 | 3篇 |
2022年 | 1篇 |
2021年 | 3篇 |
2020年 | 6篇 |
2019年 | 6篇 |
2018年 | 4篇 |
2017年 | 5篇 |
2016年 | 17篇 |
2015年 | 11篇 |
2014年 | 22篇 |
2013年 | 34篇 |
2012年 | 26篇 |
2011年 | 28篇 |
2010年 | 15篇 |
2009年 | 25篇 |
2008年 | 30篇 |
2007年 | 22篇 |
2006年 | 24篇 |
2005年 | 12篇 |
2004年 | 6篇 |
2003年 | 2篇 |
排序方式: 共有302条查询结果,搜索用时 15 毫秒
31.
32.
Sabine Gaetzner Sonja Stahl Oguzkan Sürücü Anne Schaafhausen Birgit Halliger-Keller Helmut Bertalanffy Ulrich Sure Ute Felbor 《Neurosurgical review》2007,30(2):155-160
Familial cerebral cavernous malformations (CCMs) occur with a frequency of 1 in 2000 and may cause recurrent headaches, seizures,
and hemorrhagic stroke. Exon-scanning-based methods have identified intragenic mutations in three genes, CCM1, CCM2, and CCM3, in about 70% of familial CCM. To date, only two large CCM2 and a single large CCM3 deletion have been published. In addition to direct sequencing of all three CCM genes, we applied a newly developed multiplex ligation-dependent probe amplification gene dosage assay (MLPA) designed to
detect genomic CCM1–3 deletions/duplications. Direct sequencing did not reveal a mutation in the index case who presented with multiple CCMs that
had caused a generalized tonic-clonic seizure with Todd’s paralysis and headaches at the age of 5. In contrast, MLPA analyses
detected a large deletion involving the entire CCM1 coding region in the proband and further affected members of this German CCM family. The MLPA results were corroborated by
analyses of single nucleotide polymorphisms (SNPs) within the CCM1 gene. Thus, we here present the first report on a CCM1 gene deletion. Our results confirm a loss-of-function mutation mechanism for CCM1 and demonstrate that the use of MLPA enables a higher CCM mutation detection rate which is crucial for predictive testing of at-risk relatives. 相似文献
33.
Genotype/phenotype analysis in Chinese laminin‐α2 deficient congenital muscular dystrophy patients
下载免费PDF全文
![点击此处可从《Clinical genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
S. Wang S. Song H. Yang K. Gao A. Liu H. Jiao B. Mao J. Ding X. Chang J. Wang Y. Wu Y. Yuan Y. Jiang F. Zhang H. Wu X. Wu 《Clinical genetics》2015,87(3):233-243
Laminin‐α2 deficient congenital muscular dystrophy (CMD) is an autosomal recessive disorder characterized by severe muscular dystrophy, which is typically associated with abnormal white matter. In this study, we assessed 43 CMD patients with typical white matter abnormality and laminin‐α2 deficiency (complete or partial) diagnosed by immunohistochemistry to determine the clinical and molecular genetic characteristics of laminin‐α2 deficient CMD. LAMA2 gene mutation analysis was performed by direct sequencing of genomic DNAs. Exonic deletion or duplication was identified by multiplex ligation‐dependent probe amplification (MLPA) and verified by high‐density oligonucleotide‐based CGH microarrays. Gene mutation analysis revealed 86 LAMA2 mutations (100%); 15 known and 37 novel. Among these mutations, 73.9% were nonsense, splice‐site or frameshift and 18.8% were deletions of one or more exons. Genetic characterization of affected families will be valuable in prenatal diagnosis of CMD in the Chinese population. 相似文献
34.
B. Maas D. Haas H. Sawyer S. Burton‐Jones K. Carter M. Suri M. Witsch‐Baumgartner 《Clinical genetics》2015,88(2):149-154
Pathogenic variants in the DHCR7 gene cause Smith–Lemli–Opitz syndrome (SLOS), a defect of cholesterol biosynthesis resulting in an autosomal recessive congenital metabolic malformation disorder. In approximately 4% of patients, the second mutation remains unidentified. In this study, 12 SLOS patients diagnosed clinically and/or by elevated 7‐dehydrocholesterol (7‐DHC) have been investigated by customized multiplex ligation‐dependent probe amplification (MLPA) analysis, because only one DHCR7 sequence variant has been detected. Two unrelated patients of this cohort carry different large deletions in the DHCR7 gene. One patient showed a deletion of exons 3–6. The second patient has a deletion of exons 1 and 2 (non‐coding) and lacks the major part of the promoter. These two patients show typical clinical and biochemical phenotypes of SLOS. Second disease‐causing mutations are p.(Arg352Trp) and p.(Thr93Met), respectively. Deletion breakpoints were characterized successfully in both cases. Such large deletions are rare in the DHCR7 gene but will resolve some of the patients in whom a second mutation has not been detected. 相似文献
35.
Karol Czubak Marzena Anna Lewandowska Katarzyna Klonowska Krzysztof Roszkowski Janusz Kowalewski Marek Figlerowicz Piotr Kozlowski 《Oncotarget》2015,6(27):23399-23416
A growing body of evidence indicates that miRNAs may be a class of genetic elements that can either drive or suppress oncogenesis. In this study we analyzed the somatic copy number variation of 14 miRNA genes frequently found to be either over- or underexpressed in lung cancer, as well as two miRNA biogenesis genes, DICER1 and DROSHA, in non-small-cell lung cancer (NSCLC). Our analysis showed that most analyzed miRNA genes undergo substantial copy number alteration in lung cancer. The most frequently amplified miRNA genes include the following: miR-30d, miR-21, miR-17 and miR-155. We also showed that both DICER1 and DROSHA are frequently amplified in NSCLC. The copy number variation of DICER1 and DROSHA correlates well with their expression and survival of NSCLC and other cancer patients. The increased expression of DROSHA and DICER1 decreases and increases the survival, respectively. In conclusion, our results show that copy number variation may be an important mechanism of upregulation/downregulation of miRNAs in cancer and suggest an oncogenic role for DROSHA. 相似文献
36.
37.
38.
Laura Cremonesi Maurizio Ferrari Piero C. Giordano Cornelis L. Harteveld Marina Kleanthous Thessalia Papasavva 《Hemoglobin》2013,37(3):289-311
The panoply of human globin gene mutation detection methods could become significantly enriched with the advent of microarray-based genotyping platforms. The aim of this article is to provide an overview of the current medium and high-throughput microarray-based globin gene mutation detection platforms, namely the microelectronic array, the “thalassochip” arrayed primer extension (APEX) technology and the single base extension methods. This article also outlines an emerging method based on multiple ligation probe amplification (MLPA) and discusses the implications of customized solutions for resequencing of genomic loci in relation to molecular genetic testing of hemoglobinopathies. 相似文献
39.
《Hemoglobin》2013,37(4):316-322
Deletions in the β-globin locus control region (β-LCR) lead to (εγδβ)0-thalassemia [(εγδβ)0-thal]. In patients suffering from these rare deletions, a normal hemoglobin (Hb), phenotype is found, contrasting with a hematological thalassemic phenotype. Multiplex-ligation probe amplification (MLPA) is an efficient tool to detect β-LCR deletions combined with long-range polymerase chain reaction (PCR) and DNA sequencing to pinpoint deletion breakpoints. We present here a novel 11,155 bp β-LCR deletion found in a French Caucasian patient which removes DNase I hypersensitive site 2 (HS2) to HS4 of the β-LCR. Interestingly, a 197 bp insertion of two inverted sequences issued from the HS2-HS3 inter-region is present and suggests a complex rearrangement during replication. Carriers of this type of thalassemia can be misdiagnosed as an α-thal trait. Consequently, a complete α- and β-globin gene cluster analysis is required to prevent a potentially damaging misdiagnosis in genetic counselling. 相似文献
40.