解剖学和形态学
麻醉学
听力与言语-语言病理学
行为科学
心脏和心血管系统
细胞和组织工程学
临床神经病学
危重症监护医学
牙科,口腔外科和医学
皮肤病学
急诊医学
内分泌学和新陈代谢
肠胃学和肝脏学
老人病学和老年医学
卫生保健科学和服务
血液学
免疫学
传染病
综合和补充性医学
医学伦理学
医学信息学
医学实验室技术
医学,全科和内科
医学,法律
医学,研究和试验
神经系统科学
护理
营养学和饮食学
产科医学和妇科医学
肿瘤学
眼科学
整形外科学
耳鼻喉科学
病理学
儿科学
周围血管疾病
药理学和药剂学
生理学
基本医疗保健
精神病学
公共、环境和职业卫生
放射学,核医学和医学成像
康复学
生殖生物学
呼吸系统
风湿病学
运动科学
外科学
毒理学
热带医学
泌尿学和肾脏学
病毒学
老年医学
健康政策和服务
心理学,临床
abstract::Enzymes involved in nucleic acid transactions often have a helicase-like ATPase coordinating and driving their functional activities, but our understanding of the mechanistic details of their coordination is limited. For example, DNA cleavage by the antiphage defense system Type ISP restriction-modification enzyme req...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa023
更新日期:2020-03-18 00:00:00
abstract::The cellular response to DNA double-strand breaks (DSBs) is initiated by the Mre11-Rad50-Xrs2 (MRX) complex that has structural and catalytic functions. MRX association at DSBs is counteracted by Rif2, which is known to interact with Rap1 that binds telomeric DNA through two tandem Myb-like domains. Whether and how Ra...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz1203
更新日期:2020-03-18 00:00:00
abstract::Transposable elements (TEs) comprise a large proportion of long non-coding RNAs (lncRNAs). Here, we employed CRISPR to delete a short interspersed nuclear element (SINE) in Malat1, a cancer-associated lncRNA, to investigate its significance in cellular physiology. We show that Malat1 with a SINE deletion forms diffuse...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz1176
更新日期:2020-03-18 00:00:00
abstract::Allele-specific protospacer adjacent motif (asPAM)-positioning SNPs and CRISPRs are valuable resources for gene therapy of dominant disorders. However, one technical hurdle is to identify the haplotype comprising the disease-causing allele and the distal asPAM SNPs. Here, we describe a novel CRISPR-based method (CRISP...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz1233
更新日期:2020-03-18 00:00:00
abstract::Therapeutic oligonucleotides are often modified using the phosphorothioate (PS) backbone modification which enhances stability from nuclease mediated degradation. However, substituting oxygen in the phosphodiester backbone with sulfur introduce chirality into the backbone such that a full PS 16-mer oligonucleotide is ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa031
更新日期:2020-02-28 00:00:00
abstract::I-motif DNAs have been widely employed as robust modulating components to construct reconfigurable DNA nanodevices that function well in acidic cellular environments. However, they generally display poor interactivity with fluorescent ligands under these complex conditions, illustrating a major difficulty in utilizing...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa020
更新日期:2020-02-28 00:00:00
abstract::Replication protein A (RPA) plays a critical role in all eukaryotic DNA processing involving single-stranded DNA (ssDNA). Contrary to the notion that RPA provides solely inert protection to transiently formed ssDNA, the RPA-ssDNA complex acts as a dynamic DNA processing unit. Here, we studied the diffusion of RPA alon...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz1202
更新日期:2020-02-28 00:00:00
abstract::A number of regulatory nascent peptides have been shown to regulate gene expression by causing programmed ribosome stalling during translation. Nascent peptide emerges from the ribosome through the exit tunnel, and one-third of the way along which β-loop structures of ribosomal proteins uL4 and uL22 protrude into the ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz1190
更新日期:2020-02-28 00:00:00
abstract::Type II CRISPR-Cas9 RNA-guided nucleases are widely used for genome engineering. Type II-A SpCas9 protein from Streptococcus pyogenes is the most investigated and highly used enzyme of its class. Nevertheless, it has some drawbacks, including a relatively big size, imperfect specificity and restriction to DNA targets ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz1225
更新日期:2020-02-28 00:00:00
abstract::Long Interspersed Element-1 (LINE-1) retrotransposition contributes to inter- and intra-individual genetic variation and occasionally can lead to human genetic disorders. Various strategies have been developed to identify human-specific LINE-1 (L1Hs) insertions from short-read whole genome sequencing (WGS) data; howev...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz1173
更新日期:2020-02-20 00:00:00
abstract::Release of phosphorothioate antisense oligonucleotides (PS-ASOs) from late endosomes (LEs) is a rate-limiting step and a poorly defined process for productive intracellular ASO drug delivery. Here, we examined the role of Golgi-endosome transport, specifically M6PR shuttling mediated by GCC2, in PS-ASO trafficking and...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz1171
更新日期:2020-02-20 00:00:00
abstract::Despite the large number of noncoding RNAs in human genome and their roles in many diseases include cancer, we know very little about them due to lack of structural clues. The centerpiece of the structural clues is the full RNA base-pairing structure of secondary and tertiary contacts that can be precisely obtained on...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz1192
更新日期:2020-02-20 00:00:00
abstract::Intron retention (IR) has been proposed to modulate the delay between transcription and translation. Here, we provide an exhaustive characterization of IR in differentiated white blood cells from both the myeloid and lymphoid lineage where we observed highest levels of IR in monocytes and B-cells, in addition to previ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz1180
更新日期:2020-02-20 00:00:00
abstract::G-quadruplex (G4) DNA structures are linked to key biological processes and human diseases. Small molecules that target specific G4 DNA structures and signal their presence would therefore be of great value as chemical research tools with potential to further advance towards diagnostic and therapeutic developments. Ho...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz1205
更新日期:2020-02-20 00:00:00
abstract::The enterovirus 71 (EV71) 3Dpol is an RNA-dependent RNA polymerase (RdRP) that plays the central role in the viral genome replication, and is an important target in antiviral studies. Here, we report a crystal structure of EV71 3Dpol elongation complex (EC) at 1.8 Å resolution. The structure reveals that the 5'-end gu...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz1170
更新日期:2020-02-20 00:00:00
abstract::Mitochondrial DNA (mtDNA) resides in a high ROS environment and suffers more mutations than its nuclear counterpart. Increasing evidence suggests that mtDNA mutations are not the results of direct oxidative damage, rather are caused, at least in part, by DNA replication errors. To understand how the mtDNA replicase, P...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz1018
更新日期:2020-01-24 00:00:00
abstract::RNase E is a 472-kDa homo-tetrameric essential endoribonuclease involved in RNA processing and turnover in Escherichia coli. In its N-terminal half (NTH) is the catalytic active site, as also a substrate 5'-sensor pocket that renders enzyme activity maximal on 5'-monophosphorylated RNAs. The protein's non-catalytic C-...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz1152
更新日期:2020-01-24 00:00:00
abstract::As the largest group of MYB family transcription factors, R2R3-MYB proteins play essential roles during plant growth and development. However, the structural basis underlying how R2R3-MYBs recognize the target DNA remains elusive. Here, we report the crystal structure of Arabidopsis WEREWOLF (WER), an R2R3-MYB protein...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz1081
更新日期:2020-01-10 00:00:00
abstract::Single-strand specific endoribonuclease YbeY has been shown to play an important role in the processing of the 3' end of the 16S rRNA in Escherichia coli. Lack of YbeY results in the accumulation of the 17S rRNA precursor. In contrast to a previous report, we show that Sinorhizobium meliloti YbeY exhibits endoribonucl...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz1095
更新日期:2020-01-10 00:00:00
abstract::RNA:5-methylcytosine (m5C) methyltransferases are currently the focus of intense research following a series of high-profile reports documenting their physiological links to several diseases. However, no methods exist which permit the specific analysis of RNA:m5C methyltransferases in cells. Herein, we described how a...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz1047
更新日期:2020-01-10 00:00:00
abstract::DNA2 nuclease/helicase is a structure-specific nuclease, 5'-to-3' helicase, and DNA-dependent ATPase. It is involved in multiple DNA metabolic pathways, including Okazaki fragment maturation, replication of 'difficult-to-replicate' DNA regions, end resection, stalled replication fork processing, and mitochondrial geno...
journal_title:Nucleic acids research
pub_type: 杂志文章,评审
doi:10.1093/nar/gkz1101
更新日期:2020-01-10 00:00:00
abstract::More than 200 assembly factors (AFs) are required for the production of ribosomes in yeast. The stepwise association and dissociation of these AFs with the pre-ribosomal subunits occurs in a hierarchical manner to ensure correct maturation of the pre-rRNAs and assembly of the ribosomal proteins. Although decades of re...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz1079
更新日期:2020-01-10 00:00:00
abstract::The Bovine Genome Database (BGD) (http://bovinegenome.org) has been the key community bovine genomics database for more than a decade. To accommodate the increasing amount and complexity of bovine genomics data, BGD continues to advance its practices in data acquisition, curation, integration and efficient data retrie...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz944
更新日期:2020-01-08 00:00:00
abstract::Enhancers are a class of cis-regulatory elements that can increase gene transcription by forming loops in intergenic regions, introns and exons. Enhancers, as well as their associated target genes, and transcription factors (TFs) that bind to them, are highly associated with human disease and biological processes. Alt...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz973
更新日期:2020-01-08 00:00:00
abstract::The SIGnaling Network Open Resource 2.0 (SIGNOR 2.0) is a public repository that stores signaling information as binary causal relationships between biological entities. The captured information is represented graphically as a signed directed graph. Each signaling relationship is associated to an effect (up/down-regul...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz949
更新日期:2020-01-08 00:00:00
abstract::The eukaryotic linear motif (ELM) resource is a repository of manually curated experimentally validated short linear motifs (SLiMs). Since the initial release almost 20 years ago, ELM has become an indispensable resource for the molecular biology community for investigating functional regions in many proteins. In this...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz1030
更新日期:2020-01-08 00:00:00
abstract::The PathoSystems Resource Integration Center (PATRIC) is the bacterial Bioinformatics Resource Center funded by the National Institute of Allergy and Infectious Diseases (https://www.patricbrc.org). PATRIC supports bioinformatic analyses of all bacteria with a special emphasis on pathogens, offering a rich comparative...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz943
更新日期:2020-01-08 00:00:00
abstract::Computational modelling has become increasingly common in life science research. To provide a platform to support universal sharing, easy accessibility and model reproducibility, BioModels (https://www.ebi.ac.uk/biomodels/), a repository for mathematical models, was established in 2005. The current BioModels platform ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz1055
更新日期:2020-01-08 00:00:00
abstract::MicroRNAs (miRNAs) are small noncoding RNAs that act as master regulators in many biological processes. miRNAs function mainly by downregulating the expression of their gene targets. Thus, accurate prediction of miRNA targets is critical for characterization of miRNA functions. To this end, we have developed an online...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz757
更新日期:2020-01-08 00:00:00
abstract::Carbohydrate-binding proteins play crucial roles across all organisms and viruses. The complexity of carbohydrate structures, together with inconsistencies in how their 3D structures are reported, has led to difficulties in characterizing the protein-carbohydrate interfaces. In order to better understand protein-carbo...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz860
更新日期:2020-01-08 00:00:00
abstract::The leaf senescence database (LSD) is a comprehensive resource of senescence-associated genes (SAGs) and their corresponding mutants. Through manual curation and extensive annotation, we updated the LSD to a new version LSD 3.0, which contains 5853 genes and 617 mutants from 68 species. To provide sustainable and reli...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz898
更新日期:2020-01-08 00:00:00
abstract::WormBase (https://wormbase.org/) is a mature Model Organism Information Resource supporting researchers using the nematode Caenorhabditis elegans as a model system for studies across a broad range of basic biological processes. Toward this mission, WormBase efforts are arranged in three primary facets: curation, user ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz920
更新日期:2020-01-08 00:00:00
abstract::Membraneless organelles (MOs) are dynamic liquid condensates that host a variety of specific cellular processes, such as ribosome biogenesis or RNA degradation. MOs form through liquid-liquid phase separation (LLPS), a process that relies on multivalent weak interactions of the constituent proteins and other macromole...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz848
更新日期:2020-01-08 00:00:00
abstract::Liquid-liquid phase separation plays an important role in a variety of cellular processes, including the formation of membrane-less organelles, the cytoskeleton, signalling complexes, and many other biological supramolecular assemblies. Studies on the molecular basis of phase separation in cells have focused on protei...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz978
更新日期:2019-12-16 00:00:00
abstract::RNA interference represents a potent intervention for cancer treatment but requires a robust delivery agent for transporting gene-modulating molecules, such as small interfering RNAs (siRNAs). Although numerous molecular approaches for siRNA delivery are adequate in vitro, delivery to therapeutic targets in vivo is li...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz900
更新日期:2019-12-02 00:00:00
abstract::A human telomere ends in a single-stranded 3' tail, composed of repeats of T2AG3. G-quadruplexes (GQs) formed from four consecutive repeats have been shown to possess high-structural and mechanical diversity. In principle, a GQ can form from any four repeats that are not necessarily consecutive. To understand the dyna...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz906
更新日期:2019-12-02 00:00:00
abstract::DNA predominantly contains Watson-Crick (WC) base pairs, but a non-negligible fraction of base pairs are in the Hoogsteen (HG) hydrogen bonding motif at any time. In HG, the purine is rotated ∼180° relative to the WC motif. The transitions between WC and HG may play a role in recognition and replication, but are diffi...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz837
更新日期:2019-12-02 00:00:00
abstract::Serine integrases are emerging as core tools in synthetic biology and have applications in biotechnology and genome engineering. We have designed a split-intein serine integrase-based system with potential for regulation of site-specific recombination events at the protein level in vivo. The ϕC31 integrase was split i...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz936
更新日期:2019-12-02 00:00:00
abstract::We present a multi-laboratory effort to describe the structural and dynamical properties of duplex B-DNA under physiological conditions. By processing a large amount of atomistic molecular dynamics simulations, we determine the sequence-dependent structural properties of DNA as expressed in the equilibrium distributio...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz905
更新日期:2019-12-02 00:00:00
abstract::Zar1 was one of the earliest mammalian maternal-effect genes to be identified. Embryos derived from Zar1-null female mice are blocked before zygotic genome activation; however, the underlying mechanism remains unclear. By knocking out Zar1 and its homolog Zar2 in mice, we revealed a novel function of these genes in oo...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz863
更新日期:2019-12-02 00:00:00