全文获取类型
收费全文 | 75篇 |
免费 | 6篇 |
出版年
2021年 | 7篇 |
2020年 | 1篇 |
2018年 | 2篇 |
2017年 | 2篇 |
2016年 | 3篇 |
2015年 | 2篇 |
2014年 | 2篇 |
2013年 | 2篇 |
2012年 | 5篇 |
2011年 | 5篇 |
2009年 | 4篇 |
2008年 | 2篇 |
2007年 | 2篇 |
2006年 | 2篇 |
2005年 | 1篇 |
2004年 | 1篇 |
2002年 | 3篇 |
2001年 | 2篇 |
2000年 | 2篇 |
1999年 | 1篇 |
1998年 | 10篇 |
1997年 | 2篇 |
1996年 | 2篇 |
1988年 | 1篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1977年 | 3篇 |
1976年 | 2篇 |
1972年 | 2篇 |
1971年 | 1篇 |
排序方式: 共有81条查询结果,搜索用时 31 毫秒
51.
Carbohydrate recognition by proteins is a key event in many biological
processes. Concanavalin A is known to specifically recognize the
pentasaccharide core (beta-GlcNAc-(1-->2)-alpha- Man-(1-->3)-[beta-
GlcNAc-(1-->2)-alpha-Man-(1-->6)]-Man) of N-linked oligosaccharides
with a Ka of 1.41 x 10(6 )M-1. We have determined the structure of
concanavalin A bound to beta-GlcNAc-(1-->2)-alpha-Man-(1-->3)-[beta-
GlcNAc-(1-->2)-alpha-Man- (1-->6)]-Man to 2.7A. In six of eight
subunits there is clear density for all five sugar residues and a well
ordered binding site. The pentasaccharide adopts the same conformation in
all eight subunits. The binding site is a continuous extended cleft on the
surface of the protein. Van der Waals interactions and hydrogen bonds
anchor the carbohydrate to the protein. Both GlcNAc residues contact the
protein. The GlcNAc on the 1-->6 arm of the pentasaccharide makes
particularly extensive contacts and including two hydrogen bonds. The
binding site of the 1-->3 arm GlcNAc is much less extensive.
Oligosaccharide recognition by Con A occurs through specific protein
carbohydrate interactions and does not require recruitment of adventitious
water molecules. The beta-GlcNAc-(1-->2)-Man glycosidic linkage PSI
torsion angle on the 1-->6 arm is rotated by over 50 degrees from that
observed in solution. This rotation is coupled to disruption of
interactions at the monosaccharide site. We suggest destabilization of the
monosaccharide site and the conformational strain reduces the free energy
liberated by additional interactions at the 1-->6 arm GlcNAc site.
相似文献
52.
Sandra Stefanovic‐Barrett Anna S Dickson Stephen P Burr James C Williamson Ian T Lobb Dick JH van den Boomen Paul J Lehner James A Nathan 《EMBO reports》2018,19(5)
Misfolded or damaged proteins are typically targeted for destruction by proteasome‐mediated degradation, but the mammalian ubiquitin machinery involved is incompletely understood. Here, using forward genetic screens in human cells, we find that the proteasome‐mediated degradation of the soluble misfolded reporter, mCherry‐CL1, involves two ER‐resident E3 ligases, MARCH6 and TRC8. mCherry‐CL1 degradation is routed via the ER membrane and dependent on the hydrophobicity of the substrate, with complete stabilisation only observed in double knockout MARCH6/TRC8 cells. To identify a more physiological correlate, we used quantitative mass spectrometry and found that TRC8 and MARCH6 depletion altered the turnover of the tail‐anchored protein heme oxygenase‐1 (HO‐1). These E3 ligases associate with the intramembrane cleaving signal peptide peptidase (SPP) and facilitate the degradation of HO‐1 following intramembrane proteolysis. Our results highlight how ER‐resident ligases may target the same substrates, but work independently of each other, to optimise the protein quality control of selected soluble and tail‐anchored proteins. 相似文献
53.
Catherine C Beauheim Farrell Wymore Michael Nitzberg Zachariah K Zachariah Heng Jin JH Pate Skene Catherine A Ball Gavin Sherlock 《BMC bioinformatics》2007,8(1):338
Background
Biomedical ontologies are being widely used to annotate biological data in a computer-accessible, consistent and well-defined manner. However, due to their size and complexity, annotating data with appropriate terms from an ontology is often challenging for experts and non-experts alike, because there exist few tools that allow one to quickly find relevant ontology terms to easily populate a web form. 相似文献54.
55.
Kirubhanand Chandrashekar Ponnulakshmi Rajagopal Shazia Fathima JH Saravanan Radhakrishnan Vijaya Prakash Krishnan Muthaiah Bharat Ramrao Sontakke Vishwajit Ravindra Deshmukh Vijayalakshmi Periyasamy Gayatri Girish Muthiyan Aaditya Madhusudan Tarnekar TS Gugapriya Patil Ashlesh Laxman Satyendra Chandra Tripathi Selvaraj Jayaraman 《Bioinformation》2021,17(10):866
Cissampelos pareira Linn. is a climbing herb known in Indian traditional medicine as laghupatha. It belongs to the Menispermaceae family. The enzyme glycogen phosphorylase (GP) is a promising target for the treatment of type-2 diabetes (T2DM). A variety of natural product inhibitors with both pharmaceutical and nutraceutical potential have been reported in the search for powerful, selective and drug-like GP inhibitors that could lead to hypoglycemic medicines. Therefore, it is of interest to document the molecular docking analysis data of glycogen phosphorylase with compounds from Cissampelos pareira Linn. We report the optimal binding features of 4 compounds namely Trans-N-feruloyltyramine, Coclaurine, Magnoflorine, and Curine with the target protein for further consideration in the context of T2DM. 相似文献
56.
Tineke E Buffart Melanie Louw Nicole CT van Grieken Marianne Tijssen Beatriz Carvalho Bauke Ylstra Heike Grabsch Chris JJ Mulder Cornelis JH van de Velde Schalk W van der Merwe Gerrit A Meijer 《BMC medical genomics》2011,4(1):7
Background
Infection with H. pylori is important in the etiology of gastric cancer. Gastric cancer is infrequent in Africa, despite high frequencies of H. pylori infection, referred to as the African enigma. Variation in environmental and host factors influencing gastric cancer risk between different populations have been reported but little is known about the biological differences between gastric cancers from different geographic locations. We aim to study genomic instability patterns of gastric cancers obtained from patients from United Kingdom (UK) and South Africa (SA), in an attempt to support the African enigma hypothesis at the biological level.Methods
DNA was isolated from 67 gastric adenocarcinomas, 33 UK patients, 9 Caucasian SA patients and 25 native SA patients. Microsatellite instability and chromosomal instability were analyzed by PCR and microarray comparative genomic hybridization, respectively. Data was analyzed by supervised univariate and multivariate analyses as well as unsupervised hierarchical cluster analysis.Results
Tumors from Caucasian and native SA patients showed significantly more microsatellite instable tumors (p < 0.05). For the microsatellite stable tumors, geographical origin of the patients correlated with cluster membership, derived from unsupervised hierarchical cluster analysis (p = 0.001). Several chromosomal alterations showed significantly different frequencies in tumors from UK patients and native SA patients, but not between UK and Caucasian SA patients and between native and Caucasian SA patients.Conclusions
Gastric cancers from SA and UK patients show differences in genetic instability patterns, indicating possible different biological mechanisms in patients from different geographical origin. This is of future clinical relevance for stratification of gastric cancer therapy.57.
CY X’avia Chan Anjum A Khan JH Howard Choi CM Dominic Ng Martin Cadeiras Mario Deng Peipei Ping 《Clinical proteomics》2013,10(1):7
Background
Heart failure is a multifactorial disease associated with staggeringly high morbidity and motility. Recently, alterations of multiple metabolites have been implicated in heart failure; however, the lack of an effective technology platform to assess these metabolites has limited our understanding on how they contribute to this disease phenotype. We have successfully developed a new workflow combining specific sample preparation with tandem mass spectrometry that enables us to extract most of the targeted metabolites. 19 metabolites were chosen ascribing to their biological relevance to heart failure, including extracellular matrix remodeling, inflammation, insulin resistance, renal dysfunction, and cardioprotection against ischemic injury.Results
In this report, we systematically engineered, optimized and refined a protocol applicable to human plasma samples; this study contributes to the methodology development with respect to deproteinization, incubation, reconstitution, and detection with mass spectrometry. The deproteinization step was optimized with 20% methanol/ethanol at a plasma:solvent ratio of 1:3. Subsequently, an incubation step was implemented which remarkably enhanced the metabolite signals and the number of metabolite peaks detected by mass spectrometry in both positive and negative modes. With respect to the step of reconstitution, 0.1% formic acid was designated as the reconstitution solvent vs. 6.5 mM ammonium bicarbonate, based on the comparable number of metabolite peaks detected in both solvents, and yet the signal detected in the former was higher. By adapting this finalized protocol, we were able to retrieve 13 out of 19 targeted metabolites from human plasma.Conclusions
We have successfully devised a simple albeit effective workflow for the targeted plasma metabolites relevant to human heart failure. This will be employed in tandem with high throughput liquid chromatography mass spectrometry platform to validate and characterize these potential metabolic biomarkers for diagnostic and therapeutic development of heart failure patients. 相似文献58.
Katharine M Hardy Tatiana A Yatskievych JH Konieczka Alexander S Bobbs Parker B Antin 《BMC developmental biology》2011,11(1):20
Background
FGF signalling regulates numerous aspects of early embryo development. During gastrulation in amniotes, epiblast cells undergo an epithelial to mesenchymal transition (EMT) in the primitive streak to form the mesoderm and endoderm. In mice lacking FGFR1, epiblast cells in the primitive streak fail to downregulate E-cadherin and undergo EMT, and cell migration is inhibited. This study investigated how FGF signalling regulates cell movement and gene expression in the primitive streak of chicken embryos. 相似文献59.
Camarodont sea urchins possess a rapidly evolving actin gene family whose
members are expressed in distinct cell lineages in a developmentally
regulated fashion. Evolutionary changes in the actin gene family of
echinoids include alterations in number of family members, site of
expression, and gene linkage, and a dichotomy between rapidly and slowly
evolving isoform-specific 3' untranslated regions. We present sequence
comparisons and an analysis of the actin gene family in two congeneric sea
urchins that develop in radically different modes, Heliocidaris
erythrogramma and H. tuberculata. The sequences of several actin genes from
the related species Lytechinus variegatus are also presented. We compare
the features of the Heliocidaris and Lytechinus actin genes to those of the
the actin gene families of other closely related sea urchins and discuss
the nature of the evolutionary changes among sea urchin actins and their
relationship to developmental mode.
相似文献
60.
Olivia J Conway Minerva M Carrasquillo Xue Wang Jenny M Bredenberg Joseph S Reddy Samantha L Strickland Curtis S Younkin Jeremy D Burgess Mariet Allen Sarah J Lincoln Thuy Nguyen Kimberly G Malphrus Alexandra I Soto Ronald L Walton Bradley F Boeve Ronald C Petersen John A Lucas Tanis J Ferman William P Cheshire Jay A van Gerpen Ryan J Uitti Zbigniew K Wszolek Owen A Ross Dennis W Dickson Neill R Graff-Radford Nilüfer Ertekin-Taner 《Molecular neurodegeneration》2018,13(1):53