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排序方式: 共有2158条查询结果,搜索用时 15 毫秒
71.
Thomas M Huang WS Wen D Zhu X Wang Y Metcalf CA Liu S Chen I Romero J Zou D Sundaramoorthi R Li F Qi J Cai L Zhou T Commodore L Xu Q Keats J Wang F Wardwell S Ning Y Snodgrass JT Broudy MI Russian K Iuliucci J Rivera VM Sawyer TK Dalgarno DC Clackson T Shakespeare WC 《Bioorganic & medicinal chemistry letters》2011,21(12):3743-3748
Ponatinib (AP24534) was previously identified as a pan-BCR-ABL inhibitor that potently inhibits the T315I gatekeeper mutant, and has advanced into clinical development for the treatment of refractory or resistant CML. In this study, we explored a novel series of five and six membered monocycles as alternate hinge-binding templates to replace the 6,5-fused imidazopyridazine core of ponatinib. Like ponatinib, these monocycles are tethered to pendant toluanilides via an ethynyl linker. Several compounds in this series displayed excellent in vitro potency against both native BCR-ABL and the T315I mutant. Notably, a subset of inhibitors exhibited desirable PK and were orally active in a mouse model of T315I-driven CML. 相似文献
72.
人源中和性抗汉滩病毒单克隆抗体Fab段基因的获得和表达 总被引:10,自引:5,他引:10
运用噬菌体表面表达技术,获得人源和中性抗滩滩病毒汉滩型G1基因工程单克隆抗体Fab段基因及其表达,并同时获得抗汉滩病毒核蛋白的Fab抗体。从能综合征出血热疫区恢复期病人抗凝血中分离到的外周淋巴细胞中,提取了部细胞RNA。通过RT-PCR方法,用一组人IgG Fab基因特异性引物,从合成了cDNA中经PCR扩增了一组轻链和重链Fab段基因,将轻链和重链先后插入噬菌体载体pComb3,dnalf vf 相似文献
73.
Recent studies have identified common variants in or near GC, CYP2R1 and NADSYN1/DHCR7 to be associated with 25-hydroxyvitamin D [25(OH)D] levels in European populations. We aimed to examine whether these variants
also influence 25(OH)D levels in Chinese. Seven common variants were successfully genotyped and tested for associations with
plasma 25(OH)D levels in a population-based cohort of 3,210 Chinese Hans from Beijing and Shanghai. Six common variants at
GC (rs4588, rs7041, rs2282679 and rs1155563) and NADSYN1/DHCR7 (rs3829251 and rs1790349) loci were all significantly associated with lower plasma 25(OH)D levels (−0.036 ≤ β ≤ −0.076 per risk-allele, P ≤ 5.7 × 10−5), while CYP2R1-rs2060793 showed a trend toward association with 25(OH)D levels in the Shanghai subpopulation (P = 0.08), but not in the Beijing subpopulation (P = 0.82). Haplotype-based association analyses of the four GC variants showed that only the haplotype that contained all risk-alleles (TACC) was significantly associated with lower plasma
25(OH)D levels (β = −0.085, P = 2.3 × 10−9), while the haplotype containing the risk-alleles of rs4588 and rs2282679 (TATC) was marginally associated with lower 25(OH)D
levels (β = −0.054, P = 0.0562) when compared with GCTA haplotype carrying the four protective alleles. Most notably, conditional analyses showed
that only GC-rs4588 and GC-rs2282679 (r
2 = 0.97) remained significantly associated with 25(OH)D concentrations (P ≤ 1.9 × 10−5) after adjusting for the other two SNPs in GC. In conclusion, GC and NADSYN1/DHCR7 loci individually and collectively contribute to variation in plasma vitamin D levels in Chinese Hans. 相似文献
74.
Yeast thioredoxin genes 总被引:14,自引:0,他引:14
Z R Gan 《The Journal of biological chemistry》1991,266(3):1692-1696
Based on the conserved protein sequence of thioredoxins from yeast and other organisms, two primers were synthesized for polymerase chain reaction of yeast genomic DNA. A 34-base pair (bp) sequence around the active site of yeast thioredoxin was obtained from the polymerase chain reaction product. This specific sequence was used as a probe in Southern blot analysis of total yeast genomic DNA digested with various restriction enzymes. Under conditions of high stringency, more than one DNA species hybridized with the probe, suggesting that more than one gene encodes yeast genomic library. Two Sau3A1 fragments, 825 and 2045 bp, respectively, from two different clones were cloned into pUC13. Sequence analysis of these fragments gave two different open reading frames without introns. The 825-bp Sau3A1 fragment encodes a 103-amino acid residue protein named thioredoxin I. The 2045-bp Sau3A1 fragment contains a sequence encoding thioredoxin II which has 102 amino acid residues. This is the first report of the cloning and sequencing of eukaryotic thioredoxin genes from any source. Both yeast thioredoxins contain a dithiol active site sequence, Cys-Gly-Pro-Cys. Thioredoxins I and II show 78% amino acid sequence identity. They display more amino acid sequence similarity with mammalian thioredoxin than with Escherichia coli and plant chloroplast thioredoxins. 相似文献
75.
Amplified fragment length polymorphism fingerprinting of 16 banana cultivars (Musa cvs.) 总被引:4,自引:0,他引:4
Banana is one of the most important subtropical crops. The genetic system, however, is relatively unknown and is complicated by specific interhybridization, heterozygosity, and polyploidy, which are common in most clones. These factors make identification of closely related banana cultivars difficult, particularly when sterile. Amplified fragment length polymorphism (AFLP) analysis using eight primer combinations was carried out on 16 banana cultivars. Results showed that AFLP could be used to distinguish the different cultivars by their unique banding patterns. Unique AFLP molecular markers were detected for 12 banana cultivars, which can be used to develop specific probes for identification purposes. The cluster analysis also revealed the need for a link between genotype studies using molecular techniques and the current system of classification of Musa cultivars based purely on morphological traits. 相似文献
76.
Prediction of phosphotyrosine signaling networks using a scoring matrix-assisted ligand identification approach 下载免费PDF全文
Systematic identification of binding partners for modular domains such as Src homology 2 (SH2) is important for understanding the biological function of the corresponding SH2 proteins. We have developed a worldwide web-accessible computer program dubbed SMALI for scoring matrix-assisted ligand identification for SH2 domains and other signaling modules. The current version of SMALI harbors 76 unique scoring matrices for SH2 domains derived from screening oriented peptide array libraries. These scoring matrices are used to search a protein database for short peptides preferred by an SH2 domain. An experimentally determined cut-off value is used to normalize an SMALI score, therefore allowing for direct comparison in peptide-binding potential for different SH2 domains. SMALI employs distinct scoring matrices from Scansite, a popular motif-scanning program. Moreover, SMALI contains built-in filters for phosphoproteins, Gene Ontology (GO) correlation and colocalization of subject and query proteins. Compared to Scansite, SMALI exhibited improved accuracy in identifying binding peptides for SH2 domains. Applying SMALI to a group of SH2 domains identified hundreds of interactions that overlap significantly with known networks mediated by the corresponding SH2 proteins, suggesting SMALI is a useful tool for facile identification of signaling networks mediated by modular domains that recognize short linear peptide motifs. 相似文献
77.
78.
Zekun Huang Wanlong Huang Xiaolin Liu Zhaofang Han Guangjian Liu Grace Afumwaa Boamah Yi Wang Feng Yu Yang Gan Qizhen Xiao Xuan Luo Nan Chen Meng Liu Weiwei You Caihuan Ke 《Molecular ecology resources》2022,22(1):15-27
The nautilus, commonly known as a “living fossil,” is endangered and may be at risk of extinction. The lack of genomic information hinders a thorough understanding of its biology and evolution, which can shed light on the conservation of this endangered species. Here, we report the first high-quality chromosome-level genome assembly of Nautilus pompilius. The assembled genome size comprised 785.15 Mb. Comparative genomic analyses indicated that transposable elements (TEs) and large-scale genome reorganizations may have driven lineage-specific evolution in the cephalopods. Remarkably, evolving conserved genes and recent TE insertion activities were identified in N. pompilius, and we speculate that these findings reflect the strong adaptability and long-term survival of the nautilus. We also identified gene families that are potentially responsible for specific adaptation and evolution events. Our study provides unprecedented insights into the specialized biology and evolution of N. pompilius, and the results serve as an important resource for future conservation genomics of the nautilus and closely related species. 相似文献
79.
Temple CL Tse R Bettger-Hahn M MacDermid J Gan BS Ross DC 《Plastic and reconstructive surgery》2006,117(7):2119-27; discussion 2128-30
80.
Wei Liu Yaoting Sun Weigang Ge Fangfei Zhang Lin Gan Yi Zhu Tiannan Guo Kexin Liu 《Molecular & cellular proteomics : MCP》2022,21(2):100187
Drug resistance is a critical obstacle to effective treatment in patients with chronic myeloid leukemia. To understand the underlying resistance mechanisms in response to imatinib mesylate (IMA) and adriamycin (ADR), the parental K562 cells were treated with low doses of IMA or ADR for 2 months to generate derivative cells with mild, intermediate, and severe resistance to the drugs as defined by their increasing resistance index. PulseDIA-based (DIA [data-independent acquisition]) quantitative proteomics was then employed to reveal the proteome changes in these resistant cells. In total, 7082 proteins from 98,232 peptides were identified and quantified from the dataset using four DIA software tools including OpenSWATH, Spectronaut, DIA-NN, and EncyclopeDIA. Sirtuin signaling pathway was found to be significantly enriched in both ADR-resistant and IMA-resistant K562 cells. In particular, isocitrate dehydrogenase (NADP(+)) 2 was identified as a potential drug target correlated with the drug resistance phenotype, and its inhibition by the antagonist AGI-6780 reversed the acquired resistance in K562 cells to either ADR or IMA. Together, our study has implicated isocitrate dehydrogenase (NADP(+)) 2 as a potential target that can be therapeutically leveraged to alleviate the drug resistance in K562 cells when treated with IMA and ADR. 相似文献