全文获取类型
收费全文 | 71篇 |
免费 | 4篇 |
国内免费 | 2篇 |
专业分类
综合类 | 4篇 |
化学工业 | 42篇 |
机械仪表 | 1篇 |
建筑科学 | 1篇 |
矿业工程 | 3篇 |
轻工业 | 1篇 |
水利工程 | 2篇 |
石油天然气 | 4篇 |
一般工业技术 | 3篇 |
冶金工业 | 6篇 |
自动化技术 | 10篇 |
出版年
2023年 | 1篇 |
2022年 | 20篇 |
2021年 | 21篇 |
2020年 | 2篇 |
2019年 | 1篇 |
2016年 | 2篇 |
2015年 | 1篇 |
2012年 | 3篇 |
2011年 | 3篇 |
2010年 | 3篇 |
2009年 | 1篇 |
2008年 | 1篇 |
2007年 | 1篇 |
2006年 | 3篇 |
2005年 | 2篇 |
2003年 | 2篇 |
2002年 | 1篇 |
2000年 | 4篇 |
1999年 | 1篇 |
1996年 | 1篇 |
1995年 | 2篇 |
1991年 | 1篇 |
排序方式: 共有77条查询结果,搜索用时 15 毫秒
41.
Suzanne E. de Bruijn Zeinab Fadaie Frans P. M. Cremers Hannie Kremer Susanne Roosing 《International journal of molecular sciences》2021,22(6)
The identification of pathogenic variants in monogenic diseases has been of interest to researchers and clinicians for several decades. However, for inherited diseases with extremely high genetic heterogeneity, such as hearing loss and retinal dystrophies, establishing a molecular diagnosis requires an enormous effort. In this review, we use these two genetic conditions as examples to describe the initial molecular genetic identification approaches, as performed since the early 90s, and subsequent improvements and refinements introduced over the years. Next, the history of DNA sequencing from conventional Sanger sequencing to high-throughput massive parallel sequencing, a.k.a. next-generation sequencing, is outlined, including their advantages and limitations and their impact on identifying the remaining genetic defects. Moreover, the development of recent technologies, also coined “third-generation” sequencing, is reviewed, which holds the promise to overcome these limitations. Furthermore, we outline the importance and complexity of variant interpretation in clinical diagnostic settings concerning the massive number of different variants identified by these methods. Finally, we briefly mention the development of novel approaches such as optical mapping and multiomics, which can help to further identify genetic defects in the near future. 相似文献
42.
43.
信息化的到来导致数据急剧膨胀,从大量的数据中提取有用信息并非易事,数据挖掘就是为了满足这种需要而产生的。论文介绍了数据挖掘的相关理论知识和算法,算法有关联规则、遗传算法和决策树,对这些算法进行了分析研究,并找出其局限性。 相似文献
44.
Gayle B. Collin Lanying Shi Minzhong Yu Nurten Akturk Jeremy R. Charette Lillian F. Hyde Sonia M. Weatherly Martin F. Pera Jürgen K. Naggert Neal S. Peachey Patsy M. Nishina Mark P. Krebs 《International journal of molecular sciences》2022,23(4)
Fluid and solute transporters of the retinal pigment epithelium (RPE) are core components of the outer blood–retinal barrier. Characterizing these transporters and their role in retinal homeostasis may provide insights into ocular function and disease. Here, we describe RPE defects in tvrm77 mice, which exhibit hypopigmented patches in the central retina. Mapping and nucleotide sequencing of tvrm77 mice revealed a disrupted 5’ splice donor sequence in Slc4a5, a sodium bicarbonate cotransporter gene. Slc4a5 expression was reduced 19.7-fold in tvrm77 RPE relative to controls, and alternative splice variants were detected. SLC4A5 was localized to the Golgi apparatus of cultured human RPE cells and in apical and basal membranes. Fundus imaging, optical coherence tomography, microscopy, and electroretinography (ERG) of tvrm77 mice revealed retinal detachment, hypopigmented patches corresponding to neovascular lesions, and retinal folds. Detachment worsened and outer nuclear layer thickness decreased with age. ERG a- and b-wave response amplitudes were initially normal but declined in older mice. The direct current ERG fast oscillation and light peak were reduced in amplitude at all ages, whereas other RPE-associated responses were unaffected. These results link a new Slc4a5 mutation to subretinal fluid accumulation and altered light-evoked RPE electrophysiological responses, suggesting that SLC4A5 functions at the outer blood–retinal barrier. 相似文献
45.
46.
随着市场经济的迅猛发展和全球一体化程度的加剧,许多民族本土的物质文化和非物质文化急剧消亡和流变,时代呼吁我们留住手艺,保留传统文化,使其重新焕发新的生命力。只有通过从机制到技术,从设计到产品的转变,才能将陕西关中民间织布这一陕西关中平原文化的见证,关中民间文化的瑰宝予以传承和发展。 相似文献
47.
Benjamin M. Nash Alan Ma Gladys Ho Elizabeth Farnsworth Andre E. Minoche Mark J. Cowley Christopher Barnett Janine M. Smith To Ha Loi Karen Wong Luke St Heaps Dale Wright Marcel E. Dinger Bruce Bennetts John R. Grigg Robyn V. Jamieson 《International journal of molecular sciences》2022,23(7)
The inherited retinal dystrophies (IRDs) are a clinically and genetically complex group of disorders primarily affecting the rod and cone photoreceptors or other retinal neuronal layers, with emerging therapies heralding the need for accurate molecular diagnosis. Targeted capture and panel-based strategies examining the partial or full exome deliver molecular diagnoses in many IRD families tested. However, approximately one in three families remain unsolved and unable to obtain personalised recurrence risk or access to new clinical trials or therapy. In this study, we investigated whole genome sequencing (WGS), focused assays and functional studies to assist with unsolved IRD cases and facilitate integration of these approaches to a broad molecular diagnostic clinical service. The WGS approach identified variants not covered or underinvestigated by targeted capture panel-based clinical testing strategies in six families. This included structural variants, with notable benefit of the WGS approach in repetitive regions demonstrated by a family with a hybrid gene and hemizygous missense variant involving the opsin genes, OPN1LW and OPN1MW. There was also benefit in investigation of the repetitive GC-rich ORF15 region of RPGR. Further molecular investigations were facilitated by focused assays in these regions. Deep intronic variants were identified in IQCB1 and ABCA4, with functional RNA based studies of the IQCB1 variant revealing activation of a cryptic splice acceptor site. While targeted capture panel-based methods are successful in achieving an efficient molecular diagnosis in a proportion of cases, this study highlights the additional benefit and clinical value that may be derived from WGS, focused assays and functional genomics in the highly heterogeneous IRDs. 相似文献
48.
Vasily M. Smirnov Baptiste Wilmet Marco Nassisi Christel Condroyer Aline Antonio Camille Andrieu Cline Devisme Serge Sancho Jos-Alain Sahel Christina Zeitz Isabelle Audo 《International journal of molecular sciences》2022,23(12)
Inherited retinal diseases (IRD) are a group of heterogeneous disorders, most of which lead to blindness with limited therapeutic options. Pathogenic variants in RBP4, coding for a major blood carrier of retinol, retinol-binding protein 4, are responsible for a peculiar form of IRD. The aim of this study was to investigate if retinal function of an RBP4-related IRD patient can be improved by retinol administration. Our patient presented a peculiar white-dot retinopathy, reminiscent of vitamin A deficient retinopathy. Using a customized next generation sequencing (NGS) IRD panel we discovered a novel loss-of-function homozygous pathogenic variant in RBP4: c.255G >A, p.(Trp85*). Western blotting revealed the absence of RBP4 protein in the patient’s serum. Blood retinol levels were undetectable. The patient was put on a high-dose oral retinol regimen (50,000 UI twice a week). Subjective symptoms and retinal function markedly and sustainably improved at 5-months and 1-year follow-up. Here we show that this novel IRD case can be treated by oral retinol administration. 相似文献
49.
Maria Karlova Denis V. Abramochkin Ksenia B. Pustovit Tatiana Nesterova Valery Novoseletsky Gildas Loussouarn Elena Zaklyazminskaya Olga S. Sokolova 《International journal of molecular sciences》2022,23(14)
We identified a single nucleotide variation (SNV) (c.1264A > G) in the KCNQ1 gene in a 5-year-old boy who presented with a prolonged QT interval. His elder brother and mother, but not sister and father, also had this mutation. This missense mutation leads to a p.Lys422Glu (K422E) substitution in the Kv7.1 protein that has never been mentioned before. We inserted this substitution in an expression plasmid containing Kv7.1 cDNA and studied the electrophysiological characteristics of the mutated channel expressed in CHO-K1, using the whole-cell configuration of the patch-clamp technique. Expression of the mutant Kv7.1 channel in both homo- and heterozygous conditions in the presence of auxiliary subunit KCNE1 results in a significant decrease in tail current densities compared to the expression of wild-type (WT) Kv7.1 and KCNE1. This study also indicates that K422E point mutation causes a dominant negative effect. The mutation was not associated with a trafficking defect; the mutant channel protein was confirmed to localize at the cell membrane. This mutation disrupts the poly-Lys strip in the proximal part of the highly conserved cytoplasmic A–B linker of Kv7.1 that was not shown before to be crucial for channel functioning. 相似文献
50.
Fabian A. Garces Jessica F. Scortecci Robert S. Molday 《International journal of molecular sciences》2021,22(1)
ABCA4 is an ATP-binding cassette (ABC) transporter expressed in photoreceptors, where it transports its substrate, N-retinylidene-phosphatidylethanolamine (N-Ret-PE), across outer segment membranes to facilitate the clearance of retinal from photoreceptors. Mutations in ABCA4 cause Stargardt macular degeneration (STGD1), an autosomal recessive disorder characterized by a loss of central vision and the accumulation of bisretinoid compounds. The purpose of this study was to determine the molecular properties of ABCA4 variants harboring disease-causing missense mutations in the transmembrane domains. Thirty-eight variants expressed in culture cells were analyzed for expression, ATPase activities, and substrate binding. On the basis of these properties, the variants were divided into three classes: Class 1 (severe variants) exhibited significantly reduced ABCA4 expression and basal ATPase activity that was not stimulated by its substrate N-Ret-PE; Class 2 (moderate variants) showed a partial reduction in expression and basal ATPase activity that was modestly stimulated by N-Ret-PE; and Class 3 (mild variants) displayed expression and functional properties comparable to normal ABCA4. The p.R653C variant displayed normal expression and basal ATPase activity, but lacked substrate binding and ATPase activation, suggesting that arginine 653 contributes to N-Ret-PE binding. Our classification provides a basis for better understanding genotype–phenotype correlations and evaluating therapeutic treatments for STGD1. 相似文献