全文获取类型
收费全文 | 477篇 |
免费 | 47篇 |
国内免费 | 1篇 |
专业分类
耳鼻咽喉 | 2篇 |
儿科学 | 13篇 |
妇产科学 | 2篇 |
基础医学 | 58篇 |
口腔科学 | 16篇 |
临床医学 | 22篇 |
内科学 | 10篇 |
皮肤病学 | 344篇 |
神经病学 | 3篇 |
特种医学 | 1篇 |
外科学 | 26篇 |
综合类 | 11篇 |
预防医学 | 1篇 |
眼科学 | 2篇 |
药学 | 11篇 |
中国医学 | 2篇 |
肿瘤学 | 1篇 |
出版年
2023年 | 20篇 |
2022年 | 19篇 |
2021年 | 24篇 |
2020年 | 27篇 |
2019年 | 30篇 |
2018年 | 30篇 |
2017年 | 18篇 |
2016年 | 17篇 |
2015年 | 8篇 |
2014年 | 16篇 |
2013年 | 23篇 |
2012年 | 15篇 |
2011年 | 22篇 |
2010年 | 27篇 |
2009年 | 14篇 |
2008年 | 23篇 |
2007年 | 12篇 |
2006年 | 21篇 |
2005年 | 14篇 |
2004年 | 17篇 |
2003年 | 16篇 |
2002年 | 14篇 |
2001年 | 9篇 |
2000年 | 8篇 |
1999年 | 17篇 |
1998年 | 8篇 |
1997年 | 7篇 |
1996年 | 6篇 |
1995年 | 3篇 |
1994年 | 1篇 |
1993年 | 8篇 |
1992年 | 6篇 |
1991年 | 3篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1988年 | 3篇 |
1987年 | 4篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 2篇 |
1983年 | 3篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1979年 | 2篇 |
1977年 | 1篇 |
排序方式: 共有525条查询结果,搜索用时 109 毫秒
1.
《European journal of medical genetics》2021,64(12):104345
BackgroundEpidermolysis bullosa (EB) is a genodermatosis characterized by skin fragility and blisters with variable severity. Patients with Dystrophic EB (DEB) or Junctional EB (JEB) mainly present to clinic due to greater functional impairment. Pathogenic sequence variations in COL7A1 are implicated in DEB.ObjectiveWe have tried to decipher the molecular spectrum and genotype phenotype correlation of 21 Indian patients with EB.MethodsNext generation sequencing (NGS) was performed to determine the pathogenic variants. Sanger sequencing was also done for validation of the variants in eleven individuals.ResultsPathogenic variants were detected in 20 individuals (diagnostic yield of 95%). Majority of them (90%) had sequence variation in COL7A1 while two had pathogenic variants in ITGB4 and KRT14 respectively. Out of the 18 patients confirmed to have DEB, 3 had Dominant DEB (DDEB) whereas 15 patients had Recessive DEB (RDEB). Amongst 23 sequence variations identified, 12 were found to be novel (3 were missense, 5 were premature termination codon variants while 4 were splice-site changes).ConclusionGenotype phenotype correlation was noted with milder manifestations in those with dominant inheritance types. Exact molecular diagnosis can be ascertained by NGS in majority of cases. 相似文献
2.
Sarah E. Sheppard Laura Elizabeth Anderson Cathryn Sibbald Colleen Cotton Elizabeth Bhoj Marissa J. Perman Leslie Castelo‐Soccio 《Pediatric dermatology》2019,36(6):1007-1009
Epidermolysis bullosa simplex (EBS) is a skin fragility disorder resulting from mutations of structural proteins in the epidermis. We provide a brief report of long‐term survival and reproduction in a mother with EBS due to keratin 5 (KRT5) c.1429G > A (p.E477K) mutation, which causes a particularly severe form of the disease. 相似文献
3.
Fuying Chen Linting Huang Changcan Li Jia Zhang Weiqin Yang Beibei Zhang Huaguo Li Dan Deng Jianying Liang Jinwen Shen Zhirong Yao Ming Li 《Clinical genetics》2020,98(2):179-184
Epidermolysis bullosa (EB) is a heritable blistering disorder. We performed a next-generation sequencing-based multigene panel test and successfully predicted 100% of the EB types, including, 36 EB simplex (EBS), 13 junctional EB (JEB), 86 dystrophic EB (DEB), and 3 Kindler EB. Chinese JEB and recessive DEB (RDEB) patients have relatively mild phenotypes; for severe type separately accounts for 45.5% and 23.8%, respectively. We identified 96 novel and 49 recurrent pathogenic variants in 11 genes, although we failed to detect the second mutation in one JEB and five RDEB patients. We identified one novel p.E475K mosaic mutation in the clinically normal mother of one out of 13 EBS patients with KRT5 mutations, one recurrent p.G2034R mosaic mutation, and one novel p.G2043R mosaic mutation in the clinically normal relatives of two out of 19 dominant DEB patients. This study shows that next-generation technology could be an effective tool in diagnosing EB. 相似文献
4.
目的 探讨获得性大疱性表皮松解症(EBA)基底膜带自身抗体(BMZ—Ab)的靶抗原及其定位情况。方法 用免疫印迹(IB)、盐裂皮肤间接免疫荧光(IIF)、间接免疫电镜(IIEM)等方法检测6例EBA血清中。IgG型及IgA型BMZ—Ab识别的真表皮抗原以及抗原定位情况。结果 6例EBA血清中IgG型BMZ—Ab均结合真皮提取物中290ku蛋白,3例同时伴有结合290ku蛋白的IgA型BMZ—Ab。盐裂皮肤IIF显示BMZ真皮侧IgG线状沉积,IIEM示金颗粒沉积于BMZ致密下层,即真皮锚原纤维的Ⅶ型胶原处。结论 位于BMZ致密下层的Ⅶ型胶原是EBA中BMZ-Ab的特异性靶抗原,Ⅶ型胶原上的抗原表位可被EBA血清中IgG及IgA型BMZ—Ab识别。 相似文献
5.
M M Sudhakar Krishnan R K Jeya 《Indian Journal of Thoracic and Cardiovascular Surgery》1987,5(1):63-65
Epidermolysis bullosa is a rare hereditary skin disorder1. Oesophageal involvement in this condition is rarer still2. This presentation is one such case in which the patient presented with dysphagia and characteristic skin lesions. 相似文献
6.
In the past 5 years enormous progress have been made in our understanding of the molecular basis for a number of inherited skin diseases characterized by easy blistering of the skin and the mucous membranes after minor physical trauma. This increased fragility of the skin or its appendages is due to molecular defects in genes coding for different intra- and extracellular structural proteins which are responsible for mechanical strength at their sites of expression. These diseases encompass the group of epidermolysis bullosa and disorders of cornification such as bullous forms of ichthyosis, palmoplantar keratoderma, and pachyonychia congenita. On the basis of clinical, morphological, and ultrastructural observations the epidermolysis bullosa group has been divided into three major categories. In epidermolysis bullosa simplex blister formation appears within the basal cell layer of the epidermis, and many mutations have been found in the genes of keratin 5 and 14 which are both expressed in basal keratinocytes. Epidermolytic hyperkeratosis leads to an epidermal separation in the suprabasal cell layers. In these patients numerous point mutations have now been described in the suprabasally expressed genes of keratin 1 and 10. In ichthyosis bullosa of Siemens blisters occur in the more upper suprabasal epidermis coincidental with the expression of keratin 2e, and mutations have been detected in the corresponding gene. In epidermolytic palmoplantar hyperkeratosis the suprabasal epidermal splitting is restricted to palms and soles of the patient. In keratin 9, which reveals such an exclusive expression pattern, molecular defects have indeed been recognized. Most recently in two different clinical subtypes of pachyonychia congenita, which is characterized by defective nails and focal palmoplantar hyperkeratosis, point mutations have been found in the genes coding for keratins 6, 16, and 17. In junctional epidermolysis bullosa the separation takes place within the dermal-epidermal basement membrane at the level of the lamina lucida, and mutations have been found in three genes coding for different laminin chains, in the 4 gene of 64 integrin, and in the gene of collagen XVII. In dystrophic epidermolysis bullosa the tissue separation occurs beneath the basement membrane within the papillary dermis at the level of the anchoring fibrils, and several mutations have been identified in the collagen VII gene. The rapid unraveling of molecular defects in these disabling or even lethal inherited skin diseases makes possible a more precise and earlier prenatal diagnosis, creates new options for suitable therapeutic regimens, and even offers the hope of curing these diseases by means of somatic cell gene therapy.Abbreviations
BM
Basement membrane
-
BPAg
Bullous pemphigoid antigen
-
DEB
Dystrophic epidermolysis bullosa
-
EB
Epidermolysis bullosa
-
EBS
Epidermolysis bullosa simplex
-
EHK
Epidermolytic hyperkeratosis
-
EPPK
Epidermolytic palmoplantar keratoderma
-
IBS
Ichthyosis bullosa of Siemens
-
JEB
Junctional epidermolysis bullosa
-
KIF
Keratin intermediate filaments
-
NC
Noncollagenous domain
-
NEPPK
Nonepidermolytic palmoplantar keratoderma
-
PC
Pachyonychia congenita 相似文献
7.
Wedad Hanna Earl Silverman Lionel Boxaii Bernice R. Krafchik 《Ultrastructural pathology》1983,5(1):29-36
Epidermolysis bullosa (EB), a heterogeneous group of hereditary diseases, varies in mode of inheritance, extent, severity, and presence or absence of scarring and dystrophy. Fourteen cases (13 in infants and 1 in a young adult) were studied. Subtyping by ultrastructural findings in normal and blistered skin biopsies was as follows: EB simplex (2), EB letalis (3), EBD dominant (2), and EBD recessive (7). One case diagnosed as recessive dystrophic by electron microscopy (EM) followed a benign course with little scaring and was re-classified clinically and after reviewing the EM as dominant dystrophic. Defining the level of bulla formation by EM allowed accurate diagnosis of subtypes. In 6 patients with EBD recessive, normal and bullous skin showed collagenolysis and no anchoring fibrils. In patients with EBD dominant, rudimentary fibrils were noted in normal skin. Whether absence of anchoring fibrils is primary or secondary in these two types and the role of collagenolysis remain unresolved. 相似文献
8.
目的 探讨鼠抗人单克隆抗体LH7:2诊断营养不良型大疱性表皮松解症的意义。方法 采用间接免疫荧光法对临床诊断为营养不良型大疱性表皮松解症(DEB),分别来源于3个不同家系各1名患者,包括2名显性遗传型营养不良型大疱性表皮松解症(dominant DEB,DDEB)和1名隐性遗传型营养不良型大疱性表皮松解症(recessive DEB,RDEB)进行皮肤基底膜带(BMZ)Ⅶ型胶原检测,同时选择单纯型大疱性表皮松解症(EBS)、大疱性类天疱疮及正常人各1名做对照。结果 3名对照BMZ免疫荧光阳性,2名DDEB荧光均减弱,RDEB荧光阴性。结论 鼠抗人单克隆抗体LH7:2诊断营养不良性大疱性表皮松解症有重要意义。 相似文献
9.
L Tong P R Hodgkins J Denyer D Brosnahan J Harper I Russell-Eggitt D S Taylor D Atherton 《The British journal of ophthalmology》1999,83(3):323-326
AIMS: To describe the ophthalmic findings in a large cohort of epidermolysis bullosa (EB) patients managed in one large specialist centre. METHODS: A case note review of consecutive patients seen at Great Ormond Street Children's Hospital. Data on the dermatological disease, ophthalmic history, and examination were collected and coded onto a data sheet. RESULTS: 181 patients: 50 (28%) simplex EB; 15 (8%) junctional EB; 28 (15%) autosomal dominant dystrophic EB; 72 (40%) autosomal recessive dystrophic EB; nine patients (5%) with dystrophic EB whose inheritance could not be ascertained; and seven cases (4%) of EB that could not be classified. Ocular problems were found in 12% (n = 6) of simplex patients and 40% (n = 6) of those with junctional disease. One patient (of 28) in the autosomal dominant dystrophic group had ocular involvement and 51% (37/72) of patients in the autosomal recessive dystrophic group had ophthalmic complications: corneal (25/72), lid ectropions (3/72), lid blisters (5/72), and symblepharon (3/72). CONCLUSION: Ophthalmic complications are common in EB overall but the incidence varies widely with subtype. Ophthalmic complications are the most severe in the dystrophic recessive and junctional subtypes where there is a need for extra vigilance. The major treatment modality was use of ocular lubricants. 相似文献
10.
报告14例大疱性表皮坏死松解型药疹的治疗。以磺胺类药和解热镇痛药引起者居多,各4例。皮损面积按九分法计算,皮损面积80%以上者9例,80%以上者5例,治愈9例,死亡5例,我们认为早期使用足够剂量皮质激素类药物是有效措施。病程中注意防治感染,给予足够的液体以防止水电解质失平衡,局部治疗使用本院中药“五黄油”。 相似文献