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::Promoter design remains one of the most important considerations in metabolic engineering and synthetic biology applications. Theoretically, there are 450 possible sequences for a 50-nt promoter, of which naturally occurring promoters make up only a small subset. To explore the vast number of potential sequences, we r...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa325
更新日期:2020-07-09 00:00:00
abstract::The universal L-shaped tertiary structure of tRNAs is maintained with the help of nucleotide modifications within the D- and T-loops, and these modifications are most extensive within hyperthermophilic species. The obligate-commensal Nanoarchaeum equitans and its phylogenetically-distinct host Ignicoccus hospitalis gr...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa411
更新日期:2020-07-09 00:00:00
abstract::Functional crosstalk between histone modifications and chromatin remodeling has emerged as a key regulatory mode of transcriptional control during cell fate decisions, but the underlying mechanisms are not fully understood. Here we discover an HRP2-DPF3a-BAF epigenetic pathway that coordinates methylated histone H3 ly...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa441
更新日期:2020-07-09 00:00:00
abstract::Recently, prokaryotic riboswitches have been identified that regulate transcription in response to change of the concentration of secondary messengers. The ZMP (5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR))-sensing riboswitch from Thermosinus carboxydivorans is a transcriptional ON-switch that is involved in ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa427
更新日期:2020-07-09 00:00:00
abstract::OGG1 initiated base excision repair (BER) is the major pathway for repair of oxidative DNA base damage 8-oxoguanine (8-oxoG). Here, we report that RECQL4 DNA helicase, deficient in the cancer-prone and premature aging Rothmund-Thomson syndrome, physically and functionally interacts with OGG1. RECQL4 promotes catalytic...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa392
更新日期:2020-07-09 00:00:00
abstract::Repair of DNA double-strand breaks (DSBs) with homologous chromosomes is a hallmark of meiosis that is mediated by recombination 'bridges' between homolog axes. This process requires cooperation of DMC1 and RAD51 to promote homology search and strand exchange. The mechanism(s) regulating DMC1/RAD51-ssDNA nucleoprotein...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa406
更新日期:2020-07-09 00:00:00
abstract::The dynamic topological structure of telomeric DNA is closely related to its biological function; however, no such structural information on full-length telomeric DNA has been reported due to difficulties synthesizing long double-stranded telomeric DNA. Herein, we developed an EM-PCR and TA cloning-based approach to s...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa479
更新日期:2020-07-09 00:00:00
abstract::This work seeks to remedy two deficiencies in the current nucleic acid nanotechnology software environment: the lack of both a fast and user-friendly visualization tool and a standard for structural analyses of simulated systems. We introduce here oxView, a web browser-based visualizer that can load structures with ov...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa417
更新日期:2020-07-09 00:00:00
abstract::G-quadruplex (G4) DNA structures can form physical barriers within the genome that must be unwound to ensure cellular genomic integrity. Here, we report unanticipated roles for the Escherichia coli Rep helicase and RecA recombinase in tolerating toxicity induced by G4-stabilizing ligands in vivo. We demonstrate that R...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa442
更新日期:2020-07-09 00:00:00
abstract::With the abundant mammalian lncRNAs identified recently, a comprehensive annotation resource for these novel lncRNAs is an urgent need. Since its first release in November 2016, AnnoLnc has been the only online server for comprehensively annotating novel human lncRNAs on-the-fly. Here, with significant updates to mult...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa368
更新日期:2020-07-02 00:00:00
abstract::SynergyFinder (https://synergyfinder.fimm.fi) is a stand-alone web-application for interactive analysis and visualization of drug combination screening data. Since its first release in 2017, SynergyFinder has become a widely used web-tool both for the discovery of novel synergistic drug combinations in pre-clinical mo...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa216
更新日期:2020-07-02 00:00:00
abstract::The Galaxy HiCExplorer provides a web service at https://hicexplorer.usegalaxy.eu. It enables the integrative analysis of chromosome conformation by providing tools and computational resources to pre-process, analyse and visualize Hi-C, Capture Hi-C (cHi-C) and single-cell Hi-C (scHi-C) data. Since the last publicatio...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa220
更新日期:2020-07-02 00:00:00
abstract::Nucleotide excision repair (NER) is a major DNA repair pathway for a variety of DNA lesions. XPB plays a key role in DNA opening at damage sites and coordinating damage incision by nucleases. XPB is conserved from archaea to human. In archaea, XPB is associated with a nuclease Bax1. Here we report crystal structures o...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa324
更新日期:2020-06-19 00:00:00
abstract::Zinc finger protein with KRAB and SCAN domains 3 (ZKSCAN3) has long been known as a master transcriptional repressor of autophagy. Here, we identify a novel role for ZKSCAN3 in alleviating senescence that is independent of its autophagy-related activity. Downregulation of ZKSCAN3 is observed in aged human mesenchymal ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa425
更新日期:2020-06-19 00:00:00
abstract::Adenosine-to-inosine (A-to-I) RNA editing is a common post transcriptional modification. It has a critical role in protecting against false activation of innate immunity by endogenous double stranded RNAs and has been associated with various regulatory processes and diseases such as autoimmune and cardiovascular disea...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa305
更新日期:2020-06-19 00:00:00
abstract::Mammalian antibody switch regions (∼1500 bp) are composed of a series of closely neighboring G4-capable sequences. Whereas numerous structural and genome-wide analyses of roles for minimal G4s in transcriptional regulation have been reported, Long G4-capable regions (LG4s)-like those at antibody switch regions-remain ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa357
更新日期:2020-06-19 00:00:00
abstract::The DNA damage checkpoint halts cell cycle progression in G2 in response to genotoxic insults. Central to the execution of cell cycle arrest is the checkpoint-induced stabilization of securin-separase complex (yeast Pds1-Esp1). The checkpoint kinases Chk1 and Chk2 (yeast Chk1 and Rad53) are thought to critically contr...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa355
更新日期:2020-06-19 00:00:00
abstract::Originally identified as an RNA polymerase II interactor, Che-1/AATF (Che-1) has now been recognized as a multifunctional protein involved in cell-cycle regulation and cancer progression, as well as apoptosis inhibition and response to stress. This protein displays a peculiar nucleolar localization and it has recently...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa344
更新日期:2020-06-19 00:00:00
abstract::DNA double-strand breaks are repaired by end-joining or homologous recombination. A key-committing step of recombination is DNA end resection. In resection, phosphorylated CtIP first promotes the endonuclease of MRE11-RAD50-NBS1 (MRN). Subsequently, CtIP also stimulates the WRN/BLM-DNA2 pathway, coordinating thus both...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa273
更新日期:2020-06-04 00:00:00
abstract::Site-specific DNA double-strand breaks have been used to generate knock-in through the homology-dependent or -independent pathway. However, low efficiency and accompanying negative impacts such as undesirable indels or tumorigenic potential remain problematic. In this study, we present an enhanced reduced-risk genome ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa195
更新日期:2020-06-04 00:00:00
abstract::The detailed principles of the hierarchical folding of eukaryotic chromosomes have been revealed during the last two decades. Along with structures composing three-dimensional (3D) genome organization (chromatin compartments, topologically associating domains, chromatin loops, etc.), the molecular mechanisms that are ...
journal_title:Nucleic acids research
pub_type: 杂志文章,评审
doi:10.1093/nar/gkaa261
更新日期:2020-05-21 00:00:00
abstract::A correlation between histone acetylation and transcription has been noted for a long time, but little is known about what step(s) in the transcription cycle is influenced by acetylation. We have examined the immediate transcriptional response to histone deacetylase (HDAC) inhibition, and find that release of promoter...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa234
更新日期:2020-05-21 00:00:00
abstract::Microbial biosynthetic gene clusters are a valuable source of bioactive molecules. However, because they typically represent a small fraction of genomic material in most metagenomic samples, it remains challenging to deeply sequence them. We present an approach to isolate and sequence gene clusters in metagenomic samp...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa131
更新日期:2020-05-07 00:00:00
abstract::Chromosome conformation-capture technologies are widely used in 3D genomics; however, experimentally, such methods have high-noise limitations and, therefore, require significant bioinformatics efforts to extract reliable distal interactions. Miscellaneous undesired linear DNAs, present during proximity-ligation, repr...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa106
更新日期:2020-05-07 00:00:00
abstract::Biological and chemical DNA fragmentation generates DNA molecules with a variety of termini, including blunt ends and single-stranded overhangs. We have developed a Next Generation Sequencing (NGS) assay, XACTLY, to interrogate the termini of fragmented DNA, information traditionally lost in standard NGS library prepa...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa128
更新日期:2020-05-07 00:00:00
abstract::The genetic etiology of premature ovarian insufficiency (POI) has been well established to date, however, the role of long noncoding RNAs (lncRNAs) in POI is largely unknown. In this study, we identified a down-expressed lncRNA HCP5 in granulosa cells (GCs) from biochemical POI (bPOI) patients, which impaired DNA dama...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa127
更新日期:2020-05-07 00:00:00
abstract::Epigenetic regulation of gene expression is tightly controlled by the dynamic modification of histones by chemical groups, the diversity of which has largely expanded over the past decade with the discovery of lysine acylations, catalyzed from acyl-coenzymes A. We investigated the dynamics of lysine acetylation and cr...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa163
更新日期:2020-05-07 00:00:00
abstract::The evolution of regulatory networks in Bacteria has largely been explained at macroevolutionary scales through lateral gene transfer and gene duplication. Transcription factors (TF) have been found to be less conserved across species than their target genes (TG). This would be expected if TFs accumulate mutations fas...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa162
更新日期:2020-05-07 00:00:00
abstract::Repression of cellular reprogramming in germ cells is critical to maintaining cell fate and fertility. When germ cells mis-express somatic genes they can be directly converted into other cell types, resulting in loss of totipotency and reproductive potential. Identifying the molecular mechanisms that coordinate these ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa174
更新日期:2020-05-07 00:00:00
abstract::The development of complex methods in molecular biology is a laborious, costly, iterative and often intuition-bound process where optima are sought in a multidimensional parameter space through step-by-step optimizations. The difficulty of miniaturizing reactions under the microliter volumes usually handled in multiwe...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa079
更新日期:2020-04-17 00:00:00
abstract::Measuring minimal residual disease in cancer has applications for prognosis, monitoring treatment and detection of recurrence. Simple sequence-based methods to detect nucleotide substitution variants have error rates (about 10-3) that limit sensitive detection. We developed and characterized the performance of MASQ (m...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa090
更新日期:2020-04-17 00:00:00
abstract::Cells continuously monitor protein synthesis to prevent accumulation of aberrant polypeptides. Insufficient capacity of cellular degradative systems, chaperone shortage or high levels of mistranslation by ribosomes can result in proteotoxic stress and endanger proteostasis. One of the least explored reasons for mistra...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa068
更新日期:2020-04-17 00:00:00
abstract::The spatio-temporal organization of chromatin in the eukaryotic cell nucleus is of vital importance for transcription, DNA replication and genome maintenance. Each of these activities is tightly regulated in both time and space. While we have a good understanding of chromatin organization in space, for example in fixe...
journal_title:Nucleic acids research
pub_type: 杂志文章,评审
doi:10.1093/nar/gkaa135
更新日期:2020-04-17 00:00:00
abstract::Aberrant Notch signaling plays a pivotal role in T-cell acute lymphoblastic leukemia (T-ALL) and chronic lymphocytic leukemia (CLL). Amplitude and duration of the Notch response is controlled by ubiquitin-dependent proteasomal degradation of the Notch1 intracellular domain (NICD1), a hallmark of the leukemogenic proce...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa088
更新日期:2020-04-17 00:00:00
abstract::Three-dimensional structures have been solved for several naturally occurring RNA triple helices, although all are limited to six or fewer consecutive base triples, hindering accurate estimation of global and local structural parameters. We present an X-ray crystal structure of a right-handed, U•A-U-rich RNA triple he...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz1222
更新日期:2020-04-06 00:00:00
abstract::The hexametric T7 helicase (gp4) adopts a spiral lock-washer form and encircles a coil-like DNA (tracking) strand with two nucleotides bound to each subunit. However, the chemo-mechanical coupling mechanism in unwinding has yet to be elucidated. Here, we utilized nanotensioner-enhanced Förster resonance energy transfe...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa057
更新日期:2020-04-06 00:00:00
abstract::The determination of distances between specific points in nucleic acids is essential to understanding their behaviour at the molecular level. The ability to measure distances of 2-10 nm is particularly important: deformations arising from protein binding commonly fall within this range, but the reliable measurement of...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa086
更新日期:2020-04-06 00:00:00
abstract::Accumulating evidence has demonstrated that transcriptional regulation is affected by DNA methylation. Understanding the perturbation of DNA methylation-mediated regulation between transcriptional factors (TFs) and targets is crucial for human diseases. However, the global landscape of DNA methylation-mediated transcr...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa041
更新日期:2020-03-18 00:00:00
abstract::The human Microprocessor complex cleaves primary microRNA (miRNA) transcripts (pri-miRNAs) to initiate miRNA synthesis. Microprocessor consists of DROSHA (an RNase III enzyme), and DGCR8. DROSHA contains two RNase III domains, RIIIDa and RIIIDb, which simultaneously cleave the 3p- and 5p-strands of pri-miRNAs, respect...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa018
更新日期:2020-03-18 00:00:00
abstract::We present a new coarse grained method for the simulation of duplex DNA. The algorithm uses a generalized multi-harmonic model that can represent any multi-normal distribution of helical parameters, thus avoiding caveats of current mesoscopic models for DNA simulation and representing a breakthrough in the field. The ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa015
更新日期:2020-03-18 00:00:00