全文获取类型
收费全文 | 63篇 |
免费 | 9篇 |
国内免费 | 1篇 |
专业分类
73篇 |
出版年
2021年 | 2篇 |
2020年 | 1篇 |
2019年 | 1篇 |
2018年 | 2篇 |
2017年 | 1篇 |
2015年 | 4篇 |
2014年 | 4篇 |
2013年 | 7篇 |
2012年 | 3篇 |
2011年 | 2篇 |
2010年 | 2篇 |
2009年 | 3篇 |
2007年 | 2篇 |
2006年 | 2篇 |
2005年 | 2篇 |
2004年 | 2篇 |
2003年 | 2篇 |
2002年 | 2篇 |
2001年 | 5篇 |
2000年 | 4篇 |
1999年 | 1篇 |
1998年 | 2篇 |
1997年 | 5篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1989年 | 1篇 |
1984年 | 1篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1978年 | 1篇 |
1977年 | 3篇 |
1967年 | 1篇 |
排序方式: 共有73条查询结果,搜索用时 15 毫秒
1.
Sara Rosati Ewald TJ van den Bremer Janine Schuurman Paul WHI Parren Johannis P Kamerling Albert JR Heck 《MABS-AUSTIN》2013,5(6):917-924
Here, we describe a fast, easy-to-use, and sensitive method to profile in-depth structural micro-heterogeneity, including intricate N-glycosylation profiles, of monoclonal antibodies at the native intact protein level by means of mass spectrometry using a recently introduced modified Orbitrap Exactive Plus mass spectrometer. We demonstrate the versatility of our method to probe structural micro-heterogeneity by describing the analysis of three types of molecules: (1) a non-covalently bound IgG4 hinge deleted full-antibody in equilibrium with its half-antibody, (2) IgG4 mutants exhibiting highly complex glycosylation profiles, and (3) antibody-drug conjugates. Using the modified instrument, we obtain baseline separation and accurate mass determination of all different proteoforms that may be induced, for example, by glycosylation, drug loading and partial peptide backbone-truncation. We show that our method can handle highly complex glycosylation profiles, identifying more than 20 different glycoforms per monoclonal antibody preparation and more than 30 proteoforms on a single highly purified antibody. In analyzing antibody-drug conjugates, our method also easily identifies and quantifies more than 15 structurally different proteoforms that may result from the collective differences in drug loading and glycosylation. The method presented here will aid in the comprehensive analytical and functional characterization of protein micro-heterogeneity, which is crucial for successful development and manufacturing of therapeutic antibodies 相似文献
2.
3.
Cecilia PC Soh Alastair SR Donald James Feeney Walter TJ Morgan Winifred M Watkins 《Glycoconjugate journal》1989,6(3):319-332
The tetrasaccharides GalNAcß1-4[NeuAc2-3]Galß1-4Glc and GalNAcß1-4[NeuAc2-3]Galß1-4GlcNAc were synthesised by enzymic transfer of GalNAc from UDP-GalNAc to 3-sialyllactose (NeuAc2-3Galß1-4Glc) and 3-sialyl-N-acetyllactosamine (NeuAc2-3Galß1-4GlcNAc). The structures of the products were established by methylation and1H-500 MHz NMR spectroscopy. In Sda serological tests the product formed with 3-sialyl-N-acetyllactosamine was highly active whereas that formed with 3-sialyllactose had only weak activity. 相似文献
4.
Stability of biocatalysts 总被引:1,自引:0,他引:1
Polizzi KM Bommarius AS Broering JM Chaparro-Riggers JF 《Current opinion in chemical biology》2007,11(2):220-225
Despite their many favorable qualities, the marginal stability of biocatalysts in many types of reaction media often has prevented or delayed their implementation for industrial-scale synthesis of fine chemicals and pharmaceuticals. Consequently, there is great interest in understanding effects of solution conditions on protein stability, as well as in developing strategies to improve protein stability in desired reaction media. Recent methods include novel chemical modifications of protein, lyophilization in the presence of additives, and physical immobilization on novel supports. Rational and combinatorial protein engineering techniques have been used to yield unmodified proteins with exceptionally improved stability. Both have been aided by the development of computational tools and structure-guided heuristics aimed at reducing library sizes that must be generated and screened to identify improved mutants. The number of parameters used to indicate protein stability can complicate discussions and investigations, and care should be taken to identify whether thermodynamic or kinetic stability limits the observed stability of proteins. Although the useful lifetime of a biocatalyst is dictated by its kinetic stability, only 6% of protein stability studies use kinetic stability measures. Clearly, more effort is needed to study how solution conditions impact protein kinetic stability. 相似文献
5.
Marcelo H Ratto Louis TJ Delbaere Yvonne A Leduc Roger A Pierson Gregg P Adams 《Reproductive biology and endocrinology : RB&E》2011,9(1):24
Background
The objective of the present study was to isolate and purify the protein fraction(s) of llama seminal plasma responsible for the ovulation-inducing effect of the ejaculate. 相似文献6.
STYLIANOS MICHAIL SIMAIAKIS EVEN TJØRVE GABRIELE GENTILE ALESSANDRO MINELLI MOISIS MYLONAS 《Biological journal of the Linnean Society. Linnean Society of London》2012,105(1):146-159
The present study article examines the shapes of centipede species–area relationships (SARs) in the Mediterranean islands, compares the results of the linear form of the power model between archipelagos, discusses biological significance of the power model parameters with other taxa on the Aegean archipelago, and tests for a significant small‐island effect (SIE). We used 11 models to test the SARs and we compared the quality‐of‐fit of all candidate models. The power function ranked first and Z‐values was in the range 0.106–0.334. We assessed the presence of SIEs by fitting both a continuous and discontinuous breakpoint regression model. The continuous breakpoint regression functions never performed much better than the closest discontinuous model as a predictor of centipede species richness. We suggest that the relatively low Z‐values in our data partly reflect better dispersal abilities in centipedes than in other soil invertebrate taxa. Longer periods of isolation and more recent island formation may explain the somewhat lower constant c in the western Mediterranean islands compared to the Aegean islands. Higher breakpoint values in the western Mediterranean may also be a result of larger distance to the mainland and longer separation times. Despite the differences in the geological history and the idiosyncratic features of the main island groups considered, the overall results are quite similar and this could be assigned to the ability of centipedes to disperse across isolation barriers. © 2011 The Linnean Society of London, Biological Journal of the Linnean Society, 2012, 105 , 146–159. 相似文献
7.
Trevor J. Morin Teresa J. Broering Brett A. Leav Barbra M. Blair Kirk J. Rowley Elisabeth N. Boucher Yang Wang Peter S. Cheslock Michael Knauber David B. Olsen Steve W. Ludmerer Gyongyi Szabo Robert W. Finberg Robert H. Purcell Robert E. Lanford Donna M. Ambrosino Deborah C. Molrine Gregory J. Babcock 《PLoS pathogens》2012,8(8)
Hepatitis C virus (HCV) infection is a leading cause of liver transplantation and there is an urgent need to develop therapies to reduce rates of HCV infection of transplanted livers. Approved therapeutics for HCV are poorly tolerated and are of limited efficacy in this patient population. Human monoclonal antibody HCV1 recognizes a highly-conserved linear epitope of the HCV E2 envelope glycoprotein (amino acids 412–423) and neutralizes a broad range of HCV genotypes. In a chimpanzee model, a single dose of 250 mg/kg HCV1 delivered 30 minutes prior to infusion with genotype 1a H77 HCV provided complete protection from HCV infection, whereas a dose of 50 mg/kg HCV1 did not protect. In addition, an acutely-infected chimpanzee given 250 mg/kg HCV1 42 days following exposure to virus had a rapid reduction in viral load to below the limit of detection before rebounding 14 days later. The emergent virus displayed an E2 mutation (N415K/D) conferring resistance to HCV1 neutralization. Finally, three chronically HCV-infected chimpanzees were treated with a single dose of 40 mg/kg HCV1 and viral load was reduced to below the limit of detection for 21 days in one chimpanzee with rebounding virus displaying a resistance mutation (N417S). The other two chimpanzees had 0.5–1.0 log10 reductions in viral load without evidence of viral resistance to HCV1. In vitro testing using HCV pseudovirus (HCVpp) demonstrated that the sera from the poorly-responding chimpanzees inhibited the ability of HCV1 to neutralize HCVpp. Measurement of antibody responses in the chronically-infected chimpanzees implicated endogenous antibody to E2 and interference with HCV1 neutralization although other factors may also be responsible. These data suggest that human monoclonal antibody HCV1 may be an effective therapeutic for the prevention of graft infection in HCV-infected patients undergoing liver transplantation. 相似文献
8.
TJ Beveridge 《Biotechnic & histochemistry》2001,76(3):111-118
The Gram stain differentiates bacteria into two fundamental varieties of cells. Bacteria that retain the initial crystal violet stain (purple) are said to be 'Gram-positive,' whereas those that are decolorized and stain red with carbol fuchsin (or safranin) are said to be 'Gram-negative.' This staining response is based on the chemical and structural makeup of the cell walls of both varieties of bacteria. Gram-positives have a thick, relatively impermeable wall that resists decolorization and is composed of peptidoglycan and secondary polymers. Gram-negatives have a thin peptidoglycan layer plus an overlying lipid-protein bilayer known as the outer membrane, which can be disrupted by decolorization. Some bacteria have walls of intermediate structure and, although they are officially classified as Gram-positives because of their linage, they stain in a variable manner. One prokaryote domain, the Archaea, have such variability of wall structure that the Gram stain is not a useful differentiating tool. 相似文献
9.
Replication slippage may cause parallel evolution in the secondary structures of mitochondrial transfer RNAs 总被引:9,自引:4,他引:5
Presence of the dihydrouridine (D) stem in the mitochondrial cysteine tRNA
is unusually variable among lepidosaurian reptiles. Phylogenetic and
comparative analyses of cysteine tRNA gene sequences identify eight
parallel losses of the D-stem, resulting in D-arm replacement loops.
Sampling within the monophyletic Acrodonta provides no evidence for
reversal. Slipped-strand mispairing of noncontiguous repeated sequences
during replication or direct replication slippage can explain repeats
observed within cysteine tRNAs that contain a D-arm replacement loop. These
two mechanisms involving replication slippage can account for the loss of
the cysteine tRNA D-stem in several lepidosaurian lineages, and may
represent general mechanisms by which the secondary structures of
mitochondrial tRNAs are altered.
相似文献
10.