全文获取类型
收费全文 | 112篇 |
免费 | 6篇 |
国内免费 | 5篇 |
出版年
2023年 | 2篇 |
2021年 | 1篇 |
2020年 | 2篇 |
2019年 | 2篇 |
2018年 | 3篇 |
2017年 | 2篇 |
2016年 | 2篇 |
2015年 | 5篇 |
2014年 | 9篇 |
2013年 | 9篇 |
2012年 | 13篇 |
2011年 | 10篇 |
2010年 | 5篇 |
2009年 | 8篇 |
2008年 | 11篇 |
2007年 | 6篇 |
2006年 | 5篇 |
2005年 | 4篇 |
2004年 | 4篇 |
2003年 | 4篇 |
2002年 | 3篇 |
2001年 | 2篇 |
2000年 | 2篇 |
1999年 | 1篇 |
1998年 | 2篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1985年 | 1篇 |
1983年 | 1篇 |
排序方式: 共有123条查询结果,搜索用时 78 毫秒
51.
52.
Martin Hintersteiner Andrew J. Knox Gemma Mudd Manfred Auer 《Journal of chemical biology》2012,5(2):63-79
An array of chemical modifications have recently emerged, designed to improve the stability of natural peptides that inherently
suffer from short in vivo half-lives, thereby preventing their use as therapeutics. The resultant peptidomimetics resemble
native peptides; however, they contain synthetic elements (e.g. non-coded amino acids) which confer improved biophysical properties.
An elegant approach towards the identification of peptidomimetics is through screening of large combinatorial chemical libraries
incorporating both coded and non-coded amino acids (e.g. β amino acids). We apply here our recently developed Integrated Chemical
Biophysics (ICB) platform, which combines microscale one-bead one-compound screening with fluorescence tagging of retrieved
hit beads and subsequent affinity determination of hit compounds in homogenous solution, to the task of identifying novel
mixed α, β peptidomimetic binders for the adaptor protein SLAM-associated protein (SAP), which acts as an intracellular adapter
that transduces T and NK cell activation. An enhancement to the ICB process is introduced which enables ranking hit compounds
from single-point measurements even if the library compound is <95% pure and without HPLC purification of single-bead-derived
substance. Finally, a novel computational protocol enabling binding mode and SAR rationalisation of hit compounds is also
described which we now utilise to inform future library design. Application of the full ICB process has allowed identification
of a highly interesting motif, Ac-β3-Pro-α-pTyr, as a mimic for the −1 and −2 positions of the natural binding motif and provides a promising starting point for
further optimization towards higher-affinity SAP inhibitors with enhanced metabolic stability. 相似文献
53.
Heywood W Wang D Madgett TE Avent ND Eaton S Chitty LS Mills K 《Journal of Proteomics》2012,75(11):3248-3257
Two new biomarkers, serum amyloid-P (SAP) and plasma C1-inhibitor protein are elevated in the maternal circulation of mothers carrying Down syndrome foetuses. Much emphasis of late\ has been put on the lack of translational tests being developed following the identification of new biomarkers. We have created a single-reaction-monitoring (SRM) tandem mass spectrometry-based assay for the quantitation of these biomarkers and compared these results with an in-house developed immunofluorescence-based technique (IF). This MS-based assay is a rapid 5 min test and a simple "one pot reaction," requiring only 5μl of plasma. To evaluate the potential of SRM-based quantitation in a clinical setting, SAP and C1-inhibitor were quantitated in 38 normal and Down syndrome affected pregnancies. Plasma SAP levels in the Down's group were significantly raised at 10-14 weeks (p<0.0015) and 14-20 weeks (p<0.0001). Plasma C1-inhibitor levels were also observed significantly elevated in the Down's group (10-14 weeks, p<0.0193, 14-20 weeks, p<0.0001). Analysis using the IF technique did not show any significant elevation of plasma SAP levels or C1-inhibitor levels. This rapid and sensitive assay demonstrates the potential of multiplexed tandem MS-based quantitation of proteins in chemical pathology labs and in a more cost-effective, accurate manner than conventionally used antibody methods. 相似文献
54.
We describe here the isolation and characterization of OsiSAP8, a member of stress Associated protein (SAP) gene family from rice characterized by the presence of A20 and AN1 type Zinc
finger domains. OsiSAP8 is a multiple stress inducible gene, induced by various stresses, namely heat, cold, salt, desiccation, submergence, wounding,
heavy metals as well as stress hormone Abscisic acid. OsiSAP8 protein fused to GFP was localized towards the periphery of
the cells in the epidermal cells of infiltrated Nicotiana benthamiana leaves. Yeast two hybrid analysis revealed that A20 and AN1 type zinc-finger domains of OsiSAP8 interact with each other.
Overexpression of the gene in both transgenic tobacco and rice conferred tolerance to salt, drought and cold stress at seed
germination/seedling stage as reflected by percentage of germination and gain in fresh weight after stress recovery. Transgenic
rice plants were tolerant to salt and drought during anthesis stage without any yield penalty as compared to unstressed transgenic
plants.
OsiSAP8 is deposited in the Genbank with the Accession number AY345599. 相似文献
55.
Structural requirements for calmodulin binding to membrane-associated guanylate kinase homologs 总被引:1,自引:0,他引:1
Paarmann I Lye MF Lavie A Konrad M 《Protein science : a publication of the Protein Society》2008,17(11):1946-1954
Effector molecules such as calmodulin modulate the interactions of membrane-associated guanylate kinase homologs (MAGUKs) and other scaffolding proteins of the membrane cytoskeleton by binding to the Src homology 3 (SH3) domain, the guanylate kinase (GK) domain, or the connecting HOOK region of MAGUKs. Using surface plasmon resonance, we studied the interaction of members of all four MAGUK subfamilies--synapse-associated protein 97 (SAP97), calcium/calmodulin-dependent serine protein kinase (CASK), membrane palmitoylated protein 2 (MPP2), and zona occludens (ZO) 1--and calmodulin to determine interaction affinities and localize the binding site. The SH3-GK domains of the proteins and derivatives thereof were expressed in E. coli and purified. In all four proteins, high-affinity calmodulin binding was identified. CASK was shown to contain a Ca2+-dependent calmodulin binding site within the HOOK region, overlapping with a protein 4.1 binding site. In ZO1, a Ca2+-dependent calmodulin binding site was detected within the GK domain. The equilibrium dissociation constants for MAGUK-calmodulin interaction were found to range from 50 nM to 180 nM. Sequence analyses suggest that binding sites for calmodulin have evolved independently in at least three subfamilies. For ZO1, pulldown of GST-calmodulin was shown to occur in a calcium-dependent manner; moreover, molecular modeling and sequence analyses predict conserved basic residues to be exposed on one side of a helix. Thus, calmodulin binding appears to be a common feature of MAGUKs, and Ca2+-activated calmodulin may serve as a general regulator to affect the interactions of MAGUKs and various components of the cytoskeleton. 相似文献
56.
摘要 目的:探讨白细胞介素-6(IL-6)、降钙素原(PCT)、C反应蛋白(CRP)相关炎症因子表达水平对重症急性胰腺炎(SAP)预后的预测价值,并分析不同炎症因子表达与肠道屏障损伤的相关性。方法:选取我院2019年8月到2022年8月收治的60例SAP患者为研究对象,对所有患者进行28 d随访,将28 d内死亡的20例患者分为死亡组,将其余40例患者分为存活组,对比两组患者临床一般情况与IL-6、PCT、CRP相关炎症因子表达水平,并分析SAP预后影响的独立危险因素。随后将所有患者依照肠道屏障损伤情况进行分组,分为肠道屏障损伤组(n=42)与非肠道损伤组(n=18),对比两组患者IL-6、PCT、CRP表达水平,分析炎症因子表达水平与肠道屏障损伤的相关性,并绘制各指标诊断SAP肠道屏障损伤的ROC曲线,分析其预测肠道屏障损伤的灵敏度与特异度。结果:存活组与死亡组患者胰腺坏死、APACHEⅡ评分、发生器官衰竭情况与IL-6、PCT、CRP表达水平对比差异显著(P<0.05);PCT、CRP、APACHEⅡ评分为重症胰腺炎患者的预后不良影响因素(P<0.05);肠道屏障损伤组患者IL-6、PCT、CRP表达水平明显高于非肠道屏障损伤组(P<0.05);Spearman相关分析结果显示:IL-6、PCT、CRP与肠道屏障损伤呈正相关(P<0.05);ROC曲线分析显示:曲线下面积(AUC)从低到高依次为IL-6 (0.631)、CRP(0.667)、PCT(0.671)、联合诊断(0.852)。血清IL-6、PCT、CRP的联合诊断的灵敏度与特异度明显高于血清IL-6、PCT、CRP单一诊断(P<0.05)。结论:IL-6、PCT、CRP相关炎症因子表达水平可预测SAP患者预后情况,IL-6、PCT、CRP与SAP肠道屏障损伤呈正相关,且三者联合对SAP肠道屏障损伤的诊断具有重要价值。 相似文献
57.
Naoki Maruyama Kazuhiro Shigemoto Sachiho Kubo Setsuko Handa Naoshi Ishikawa Yohjiro Itoh Rosemary W. Elliott 《Biochemical genetics》1989,27(3-4):229-237
A full-length cDNA clone, pmSAP3, encoding the serum P component (SAP), has been used to search for DNA fragment length variation
among mouse strains previously analyzed for differences in endogenous SAP levels. Three alleles were found usingEcoRI-digested DNA. The finding of a single 5.4-kb fragment, alleled, in DNA from DBA/2J mice suggests the presence of a singleSap locus. Segregation of DNA fragment associated withSap
b
andSap
d
alleles was analyzed in three sets of recombinant inbred (RI) strains. The strain distribution pattern found for theSap alleles was identical to that of alleles ofLy-9 in 43 individual RI strains, suggesting tight linkage withLy-9 on mouse chromosome 1. In the BXD RI strains, the SDP of theSap locus, defined by the difference in the endogenous SAP level, is also identical to the SDP of the DNA fragments. We propose
to redesignate theSap locus to include both the structural element defined by the DNA polymorphism and the regulatory element involved in the regulation
of SAP synthesis. TheSap locus is the major genetic element contributing to the regulation of SAP production. Other genetic factors are also involved,
as shown by the presence of nonparental phenotypes in the individual BXH RI strains.
This study was performed through special Coordination Funds of the Science and Technology Agency of the Japanese Government
and PHS Grant GM24464 to R.W.E. 相似文献
58.
Yinxian Wen Jun Qin Yu Deng Hui Wang Jacques Magdalou Liaobin Chen 《Biochemical and biophysical research communications》2014
UDP-galactose-4-epimerase (GALE) is a key enzyme catalyzing the interconversion of UDP-glucose and UDP-galactose, as well as UDP-N-acetylglucosamine and UDP-N-acetylgalactosamine, which are all precursors for the proteoglycans (PGs) synthesis. However, whether GALE is essential in cartilage homeostasis remains unknown. Therefore, we investigated the role of GALE in PGs synthesis of human articular chondrocytes, the GALE expression in OA, and the regulation of GALE expression by interleukin-1beta (IL-1β). Silencing GALE gene with specific siRNAs resulted in a markedly inhibition of PGs synthesis in human articular chondrocytes. GALE protein levels were also decreased in both human and rat OA cartilage, thus leading to losses of PGs contents. Moreover, GALE mRNA expression was stimulated by IL-1β in early phase, but suppressed in late phase, while the suppression of GALE expression induced by IL-1β was mainly mediated by stress-activated protein kinase/c-Jun N-terminal kinase pathway. These data indicated a critical role of GALE in maintaining cartilage homeostasis, and suggested that GALE inhibition might contribute to OA progress. 相似文献
59.
Guihua Lu Shuang Xu Longyun Peng Zhibin Huang Yesong Wang Xiuren Gao 《Biochemical and biophysical research communications》2014
Kv1.5 potassium channel represents a promising target for atrial fibrillation (AF) therapy. During AF, the renin–angiotensin system is markedly activated. Recent evidence indicates that angiotensin II (Ang II) can upregulate Kv1.5 channel, but the mechanism remains unknown. In this study, we report that Ang II-mediated transforming growth factor-beta1 (TGF-β1)/Smad2/3 and extracellular signal-regulated kinase (ERK) 1/2 signalings are involved in atrial Kv1.5 expression. In neonatal rat atrial myocytes, quantitative PCR and Western blotting revealed that Ang II upregulated TGF-β1, synapse-associated protein 97 (SAP97) and Kv1.5 expression in a time- and concentration-dependent manner. The Ang II-induced upregulation of Kv1.5, SAP97 and phosphorylated Smad2/3 (P-Smad2/3) were reversed by the Ang II type 1 (AT1) receptor antagonist losartan, an anti-TGF-β1 antibody and the ERK 1/2 inhibitor PD98059 but not by the AT2 receptor antagonist PD123319. mRNA knockdown of either Smad2 or Smad3 blocked Ang II-induced expression of Kv1.5 and SAP97. These data suggest that AT1 receptor/TGF-β1/P-Smad2/3 and ERK 1/2 signalings are involved in Ang II-induced Kv1.5 and SAP97 expression. Flow cytometry and Western blotting revealed that losartan and the anti-TGF-β1 antibody diminished Ang II-induced reactive oxygen species (ROS) generation and that the antioxidants diphenyleneiodonium and N-acetyl cysteine inhibited Ang II-induced expression of P-Smad2/3, phosphorylated ERK (P-ERK) 1/2, Kv1.5, SAP97, suggesting that ROS participate in Kv1.5 and SAP97 regulation by modulating Ang II-induced P-Smad2/3 and P-ERK 1/2 expression. In conclusion, we demonstrate that ROS-dependent Ang II/AT1 receptor/TGF-β1/P-Smad2/3 and Ang II/ERK 1/2 signalings are involved in atrial Kv1.5 and SAP97 expression. Antioxidants would be beneficial for AF treatment through inhibiting atrial Kv1.5 expression. 相似文献
60.
目的:探讨重症胰腺炎患者采用生长抑素联合奥美拉唑治疗的临床效果。方法:选取2005年10月至2012年10月医院收治的老年重症胰腺炎患者98例。将所有患者随机分为观察组和对照组,每组各49例,对照组患者采取常规方法治疗重症胰腺炎,观察组患者在此基础上加用生长抑素联合奥美拉唑进行治疗。两组患者的疗程均为7天,治疗结束后,对两组患者的临床疗效、各项恢复指标和并发症等情况进行对比分析。结果:观察组患者治疗的总有效率显著高于对照组(93.9%vs.71.4%,P0.05);观察组患者的平均住院、肠道恢复、腹痛腹胀缓解、血淀粉酶、尿淀粉酶等各项指标恢复至正常时间及预后均显著优于对照组,差异具有统计学意义(P0.05)。结论:采用生长抑素联合奥美拉唑治疗重症胰腺炎,可以获得更高的疗效,患者症状改善明显,治疗时间短,并发症少,死亡率低,值得临床推广。 相似文献