全文获取类型
收费全文 | 453篇 |
免费 | 21篇 |
出版年
2024年 | 1篇 |
2023年 | 5篇 |
2022年 | 3篇 |
2021年 | 13篇 |
2020年 | 4篇 |
2019年 | 13篇 |
2018年 | 12篇 |
2017年 | 8篇 |
2016年 | 15篇 |
2015年 | 26篇 |
2014年 | 20篇 |
2013年 | 26篇 |
2012年 | 35篇 |
2011年 | 47篇 |
2010年 | 18篇 |
2009年 | 12篇 |
2008年 | 21篇 |
2007年 | 24篇 |
2006年 | 30篇 |
2005年 | 12篇 |
2004年 | 24篇 |
2003年 | 24篇 |
2002年 | 21篇 |
2001年 | 4篇 |
2000年 | 4篇 |
1999年 | 4篇 |
1998年 | 3篇 |
1997年 | 3篇 |
1994年 | 1篇 |
1992年 | 5篇 |
1991年 | 2篇 |
1989年 | 2篇 |
1988年 | 4篇 |
1986年 | 1篇 |
1985年 | 3篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1980年 | 4篇 |
1979年 | 4篇 |
1977年 | 3篇 |
1974年 | 3篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1955年 | 2篇 |
1954年 | 1篇 |
排序方式: 共有474条查询结果,搜索用时 15 毫秒
1.
2.
Analysis of the human regulators of complement activation (RCA) gene cluster with yeast artificial chromosomes (YACs). 总被引:6,自引:0,他引:6
D Hourcade A D Garcia T W Post P Taillon-Miller V M Holers L M Wagner N S Bora J P Atkinson 《Genomics》1992,12(2):289-300
The human regulators of complement activation gene cluster (RCA cluster) have been partially characterized with yeast artificial chromosomes (YACs). While the data confirm many points previously elucidated, the finer resolution of YAC mapping has allowed the discovery and/or localization of partial gene duplications, the determination of gene orientations, and the measurement of gaps between known genes. Here nine overlapping YACs that encompass a genomic region of 800 kb, encoding four RCA genes and three gene-like elements, are described. The encoded genes and two of the gene-like elements share the same orientation and are ordered (5' to 3') DAF, CR2, CR1, MCP-like, CR1-like, and MCP. A C4bp-like region lies upstream from DAF and is likely to correspond to one recently observed by F. Pardo-Manuel, J. Rey-Campos, A. Hillarp, B. Dahlback, and S. Rodriguez de Cordoba (1990, Proc. Natl. Acad. Sci. USA 87: 4529-4533). MCP-like, a new genetic element, was discovered and found to be homologous to the 5' portion of the MCP gene. Two large gaps of 85 kb (between CR2 and DAF) and 110 kb (between DAF and the C4bp-like element) could carry additional RCA genes. The arrangement of CR1, MCP-like, CR1-like, and MCP, in that order, strongly suggests that this region was generated by a single duplication of neighboring CR1/CR1-like and MCP/MCP-like forerunners. The RCA YACs will now serve as convenient DNA sources for the subcloning and further characterization of this region. 相似文献
3.
Short-term metabolic and concomitant morphologic effects of streptozotocin diabetes on isoproterenol-induced myocardial infarction
was studied in Wistar rats, Of particular significance was the observation that myocardial infarction in concert with diabetes
brought about a distinctive exacerbation of the severity and complexity of the histopathological lesions. Of all the biochemical
parameters, serum glucose and free fatty acids registered maximum elevation and serum lactate and cardiac glycogen levels
a maximum reduction. Among the lipoproteins, an inverse relationship was found between high density lipoproteins and low density
and very low density lipoproteins; while high density lipoproteins, ratio of high density lipoprotein to low density lipoprotein
and the percentage of high density lipoprotein were decreased, there was a significant increase in low density lipoprotein
concentration and percentage values of low density and very low density lipoproteins. In diabetes, the B cell of the endocrine
pancreas depicted selective necrosis. Loss of insulin granules and wide-spread necrobiosis of cellular elements of the pancreatic
islets were observed, respectively, in myocardial infarction and in diabetes plus myocardial infarction combinations. Pathological
evidence of chemical-induced mild toxicity was present in the exocrine parenchyma. Mitotic features and the presence of centroacinar
cells in the damaged Langerhans’ islets supposedly formed the basis of regeneration of the tissue in diabetes, with or without
vascular complications 相似文献
4.
Haemoglobin binding with haptoglobin. Localization of the haptoglobin-binding site on the alpha-chain of human haemoglobin. 总被引:2,自引:2,他引:0
下载免费PDF全文
![点击此处可从《The Biochemical journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
A synthetic approach was employed to identify the haptoglobin-binding site on the alpha-chain of human haemoglobin. This approach cosists of the synthesis of a series of consecutive overlapping peptides that, together, systematically represent the entire protein chain. Fourteen peptides were synthesized (alpha 1-15, alpha 11-25, alpha 21-35, alpha 31-45, alpha 41-55, alpha 51-65, alpha 61-75, alpha 71-85, alpha 81-95, alpha 91-105, alpha 101-115, alpha 111-125, alpha 121-135 and alpha 131-141), and their ability bind human haptoglobin was studied, Only peptide alpha 121-135 bound haptoglobin significantly. On this basis we conclude that the haptoglobin-binding site on the alpha-chain of haemoglobin resides within, but does not necessarily encompass all of, the region alpha 121-135. 相似文献
5.
Localization and verification by synthesis of five antigenic sites of bovine serum albumin. 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《The Biochemical journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Recently we have shown that the major antigenic sites of bovine serum albumin exhibit functional equivalence progessively increasing with the time at which antibodies are obtained after the first immunization. Analysis of our recent immunochemical findings and the known covalent structure of bovine serum albumin have enabled us to predict the locations of five antigenic sites of bovine serum albumin. The predicted locations were synthesized, and immunochemical studies with late-course antisera showed them to constitute antigenic sites of native bovine serum albumin. 相似文献
6.
7.
Ximing Du Abdulla S. Kazim Ian W. Dawes Andrew J. Brown Hongyuan Yang 《Traffic (Copenhagen, Denmark)》2013,14(1):107-119
The exit of low‐density lipoprotein derived cholesterol (LDL‐C) from late endosomes (LE)/lysosomes (Ly) is mediated by Niemann–Pick C1 (NPC1), a multipass integral membrane protein on the limiting membranes of LE/Ly, and by NPC2, a cholesterol‐binding protein in the lumen of LE/Ly. NPC2 delivers cholesterol to the N‐terminal domain of NPC1, which is believed to insert cholesterol into the limiting membrane for subsequent transport to other subcellular organelles. Few cytoplasmic factors have been identified to govern cholesterol efflux from LE/Ly, and much less is known about the underlying molecular mechanisms. Here we establish VPS4, an AAA ATPase that has a well‐established role in disassembling the ESCRT (endosomal sorting complex required for transport)‐III polymer, as an important regulator of endosomal cholesterol transport. Knocking down VPS4 in HeLa cells resulted in prominent accumulation of LDL‐C in LE/Ly, and disrupted cholesterol homeostatic responses at the endoplasmic reticulum. The level and localization of NPC1 and NPC2 appeared to be normal in VPS4 knockdown cells. Importantly, depleting any of the ESCRT‐III components did not exert a significant effect on endosomal cholesterol transport. Our results thus identify an important cytoplasmic regulator of endosomal cholesterol trafficking and represent the first functional separation of VPS4 from ESCRT‐III. 相似文献
8.
Migyeong Jo Sanghwan Ko Bora Hwang Sung-Won Min Ji Yeon Ha Ji Chul Lee Se-Eun Jang Sang Taek Jung 《Biotechnology and bioengineering》2020,117(8):i-i
The immunoglobulin G (IgG) molecule has a long circulating serum half-life (~3 weeks) through pH- dependent FcRn binding-mediated recycling. To hijack the intracellular trafficking and recycling mechanism of IgG as a way to extend serum persistence of non-antibody therapeutic proteins, we have evolved the ectodomain of a low-affinity human FcγRIIa for enhanced binding to the lower hinge and upper CH2 region of IgG, which is very far from the FcRn binding site (CH2–CH3 interface). High-throughput library screening enabled isolation of an FcγRIIa variant (2A45.1) with 32-fold increased binding affinity to human IgG1 Fc (equilibrium dissociation constant: 9.04 × 10−7 M for wild type FcγRIIa and 2.82 × 10−8 M for 2A45.1) and significantly improved affinity to mouse serum IgG compared to wild type human FcγRIIa. The in vivo pharmacokinetic profile of PD-L1 fused with engineered FcγRIIa (PD-L1–2A45.1) was compared with that of PD-L1 fused with wild type FcγRIIa (PD-L1–wild type FcγRIIa) and human PD-L1 in mice. PD-L1–2A45.1 showed 11.7- and 9.7-fold prolonged circulating half-life (t1/2) compared to PD-L1 when administered intravenously and intraperitoneally, respectively. In addition, the AUCinf of PD-L1–2A45.1 was two-fold higher compared to that of PD-L1–wild type FcγRIIa. These results demonstrate that engineered FcγRIIa fusion offers a novel and successful strategy for prolonging serum half-life of therapeutic proteins. 相似文献
9.
Arzu Ozgen Kazim Sezen Ismail Demir Zihni Demirbag Remziye Nalcacioglu 《Current microbiology》2013,67(4):499-504
The chitinase B (chiB) and C (chiC) genes and flanking regions from a local isolate of Serratia marcescens were cloned individually and sequenced. Results showed that these chiB and chiC genes have a 96 % maximum similarity with chiB and chiC from different S. marcescens species (GenBank numbers Z36295.1 and AJ630582.1, respectively). The amplified chiB fragment, including some upstream and downstream regions, is 1,689-bp long with an open reading frame of 1,500 bp. The amplified fragment of chiC is 1,844 bp with an open reading frame of 1,443 bp. These sequences were submitted to the GenBank with accession numbers JX847796 (chiB) and JX847797 (chiC). Putative promoter regions and Shine–Dalgarno sequences were identified in both genes. The genes were cloned into a shuttle vector and the constructs were designated as pHYSB and pHYSC, respectively. Both plasmids were introduced separately into kurstaki and israelensis strains of Bacillus thuringiensis and the insecticidal activities of the engineered B. thuringiensis strains were assayed in larvae of Galleria mellonella and adult of Drosophila melanogaster. Engineered B. thuringiensis strains showed higher insecticidal activity than parental strain and the parental S. marcescens. In addition, pHYSB and pHYSC were stable over 16 daily passages under non-selective conditions in transformed B. t. israelensis 5724 strain. 相似文献
10.
Genetic localization and in vivo characterization of a Monascus azaphilone pigment biosynthetic gene cluster 总被引:1,自引:0,他引:1