全文获取类型
收费全文 | 127篇 |
免费 | 10篇 |
出版年
2024年 | 1篇 |
2023年 | 1篇 |
2022年 | 1篇 |
2021年 | 3篇 |
2020年 | 1篇 |
2019年 | 2篇 |
2017年 | 1篇 |
2016年 | 2篇 |
2015年 | 4篇 |
2014年 | 5篇 |
2013年 | 2篇 |
2012年 | 3篇 |
2011年 | 4篇 |
2010年 | 4篇 |
2009年 | 2篇 |
2008年 | 2篇 |
2007年 | 1篇 |
2006年 | 7篇 |
2005年 | 7篇 |
2004年 | 1篇 |
2003年 | 6篇 |
2002年 | 3篇 |
2001年 | 2篇 |
2000年 | 3篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1993年 | 2篇 |
1992年 | 2篇 |
1991年 | 3篇 |
1990年 | 6篇 |
1989年 | 4篇 |
1988年 | 9篇 |
1987年 | 5篇 |
1986年 | 7篇 |
1985年 | 5篇 |
1984年 | 1篇 |
1983年 | 5篇 |
1982年 | 2篇 |
1981年 | 4篇 |
1980年 | 1篇 |
1979年 | 4篇 |
1977年 | 1篇 |
1974年 | 1篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1967年 | 2篇 |
排序方式: 共有137条查询结果,搜索用时 31 毫秒
71.
Mast cells function as the initiator of the allergic reaction and play a role in the innate immune system. Aggregation of the high affinity IgE receptor (FcepsilonRI) on mast cells triggers degranulation with the release of chemical mediators such as histamine, production of cytokines and leukotrienes. FcepsilonRI signals by activating proximal non-receptor type of protein-tyrosine kinases, Lyn, Syk, Btk and Fyn. Activated tyrosine kinases then phosphorylate their specific substrates which include other enzymes and adaptor proteins and assemble these cytoplasmic signaling molecules for cellular activation. The adaptor proteins have multiple domains that allow binding to effector molecules and therefore act as positive or negative regulators controlling FcepsilonRI signaling. Deletion of the adaptor proteins such as LAT, SLP-76 or Gab2 resulted in decreased FcepsilonRI-mediated anaphylactic reaction in vivo. Functional analysis of adaptor proteins has raised the possibility that they may be new targets for the discovery of anti-allergic drugs. 相似文献
72.
Interpretation of enantioresolution in nordeoxycholic acid channels based on the four-location model
Nordeoxycholic acid (NDCA) forms three kinds of host frameworks, M1, M2, and M3, with channels where aliphatic alcohols (1-7) are accommodated. (13)C-NMR studies clarified that racemic alcohols 1- or 2-6 are enclosed in the M1- or M2-type channel with lower than 15% enantiomeric excess, respectively, while 3-methyl-2-pentanol (7) is done in the M3-type with 47% ee. These inclusion phenomena can be explained due to the Difference Fourier maps of electron densities of their enantiomers in the channels. In addition, analysis of the manner of packing indicates that four locations in the channels should be fixed for the enantioresolution of the alcohols. These results support the four-location model, which has been proposed by Mesecar et al.(20) with respect to enantioresolution on protein surfaces. 相似文献
73.
Sada Nand Pandey Naseer Iqbal Prashant K. Singh Nilisha Rastogi Punit Kaur Sujata Sharma Tej P. Singh 《Proteins》2019,87(2):99-109
Ribosome inactivating protein (RIP) catalyzes the cleavage of glycosidic bond formed between adenine and ribose sugar of ribosomal RNA to inactivate ribosomes. Previous structural studies have shown that RNA bases, adenine, guanine, and cytosine tend to bind to RIP in the substrate binding site. However, the mode of binding of uracil with RIP was not yet known. Here, we report crystal structures of two complexes of type 1 RIP from Momordica balsamina (MbRIP1) with base, uracil and nucleoside, uridine. The binding studies of MbRIP1 with uracil and uridine as estimated using fluorescence spectroscopy showed that the equilibrium dissociation constants (KD) were 1.2 × 10−6 M and 1.4 × 10−7 M respectively. The corresponding values obtained using surface plasmon resonance (SPR) were found to be 1.4 × 10−6 M and 1.1 × 10−7 M, respectively. Structures of the complexes of MbRIP1 with uracil (Structure-1) and uridine (Structure-2) were determined at 1.70 and 1.98 Å resolutions respectively. Structure-1 showed that uracil bound to MbRIP1 at the substrate binding site but its mode of binding was significantly different from those of adenine, guanine and cytosine. However, the mode of binding of uridine was found to be similar to those of cytidine. As a result of binding of uracil to MbRIP1 at the substrate binding site, three water molecules were expelled while eight water molecules were expelled when uridine bound to MbRIP1. 相似文献
74.
Shota Yamauchi Kenji Takeuchi Kazuyasu Chihara Xuedong Sun Chisato Honjoh Hatsumi Yoshiki Hak Hotta Kiyonao Sada 《The Journal of biological chemistry》2015,290(36):21857-21864
Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is thought to regulate the replication of viral RNA and the assembly of virus particles in a serine/threonine phosphorylation-dependent manner. However, the host kinases that phosphorylate NS5A have not been fully identified. Here, we show that HCV particle assembly involves the phosphorylation of NS5A by the c-Abl tyrosine kinase. Pharmacological inhibition or knockdown of c-Abl reduces the production of infectious HCV (J6/JFH1) particles in Huh-7.5 cells without markedly affecting viral RNA translation and replication. NS5A is tyrosine-phosphorylated in HCV-infected cells, and this phosphorylation is also reduced by the knockdown of c-Abl. Mutational analysis reveals that NS5A tyrosine phosphorylation is dependent, at least in part, on Tyr330 (Tyr2306 in polyprotein numbering). Mutation of this residue to phenylalanine reduces the production of infectious HCV particles but does not affect the replication of the JFH1 subgenomic replicon. These findings suggest that c-Abl promotes HCV particle assembly by phosphorylating NS5A at Tyr330. 相似文献
75.
K Sakai S Nakamura K Sada T Kobayashi H Uno H Yamamura 《Biochemical and biophysical research communications》1988,152(3):1123-1130
Biochemical properties of a cytosolic protein-tyrosine kinase (CPTK-40) partially purified from porcine spleen were characterized and compared with p40 kinase, a cytosolic protein-tyrosine kinase from bovine thymus. When CPTK-40 was incubated with MnCl2 and (gamma-32P)ATP, only a phosphoprotein with a molecular weight of 40 kilodalton was observed. CPTK-40 efficiently phosphorylated tubulin with the rate of 0.5 nmol/min/mg. Unlike p40 kinase, casein was also a substrate for CPTK-40. Among various divalent cations tested, Co2+, Mn2+ and Mg2+ were effective metal ions for the enzyme activity. Ca2+ could also serve as a divalent cation for the activity although the rate was low. These results suggest that CPTK-40 is similar but not identical to p40 kinase. 相似文献
76.
Anggraeni E. Kusumaningrum Sarce Makaba Eyhab Ali Mandeep Singh Mohammed N. Fenjan Irodakhon Rasulova Neeti Misra Sada G. Al- Musawi Ali Alsalamy 《Cell biochemistry and function》2024,42(1):e3906
The majority of cancer cases are colorectal cancer, which is also the second largest cause of cancer-related deaths worldwide. Metastasis is the leading cause of death for patients with colorectal cancer. Metastatic colorectal cancer incidence are on the rise due to a tiny percentage of tumors developing resistant to medicines despite advances in treatment tactics. Cutting-edge targeted medications are now the go-to option for customized and all-encompassing CRC care. Specifically, multitarget kinase inhibitors, antivascular endothelial growth factors, and epidermal growth factor receptors are widely used in clinical practice for CRC-targeted treatments. Rare targets in metastatic colorectal cancer are becoming more well-known due to developments in precision diagnostics and the extensive use of second-generation sequencing technology. These targets include the KRAS mutation, the BRAF V600E mutation, the HER2 overexpression/amplification, and the MSI-H/dMMR. Incorporating certain medications into clinical trials has significantly increased patient survival rates, opening new avenues and bringing fresh viewpoints for treating metastatic colorectal cancer. These focused therapies change how cancer is treated, giving patients new hope and better results. These markers can significantly transform and individualize therapy regimens. They could open the door to precisely customized and more effective medicines, improving patient outcomes and quality of life. The fast-growing body of knowledge regarding the molecular biology of colorectal cancer and the latest developments in gene sequencing and molecular diagnostics are directly responsible for this advancement. 相似文献
77.
78.
Yuzuru Kobayashi Tomonori Tamai Takashi Oyama Hitoshi Hasegawa Eiji Sada Tomohiro Kusaba Masaharu Hamaji 《Microbiology and immunology》1984,28(3):359-370
Monoclonal antibodies against etiological agents of Weil's disease were produced by cell fusion technology. Twenty hybridomas were produced through the fusion of P3×63Ag8.653 cells with spleen cells from BALB/c mice immunized against Leptospira interrogans serovar icterohaemorrhagiae RGA strain and serovar copenhageni Shiromizu and M20 strains. Reactivities of the antibodies produced by the hybridomas were determined by the microscopic agglutination test. Among the five hybridoma antibodies to the RGA strain, two reacted specifically to serovar icterohaemorrhagiae, two reacted to serovar icterohaemorrhagiae at a high titer and serovar copenhageni at a low titer, and one reacted to serovars icterohaemorrhagiae, copenhageni, pyrogenes, and canicola. Of the ten hybridoma antibodies to the Shiromizu strain, one reacted specifically to serovar copenhageni, seven reacted to both serovars copenhageni and icterohaemorrhagiae at almost the same titer, and two exhibited intermediate properties. Of the five hybridoma antibodies to the M20 strain, three reacted to both serovars copenhageni and icterohaemorrhagiae at almost the same titer, one reacted to serovar copenhageni at a low titer and serovar icterohaemorrhagiae at a high titer, and one reacted to serovars copenhageni, icterohaemorrhagiae, and pyrogenes. The results revealed that each serovar has its own antigen(s) and their common antigens. In addition, 20 strains of leptospires were recently isolated and tested with three monoclonal antibodies characterized by different reactivities. Twenty strains were clearly identified by their antibodies, i.e., 16 strains were identified as serovar icterohaemorrhagiae and three strains were identified as serovar copenhageni. The remaining strain, which was not agglutinated by three antibodies, was identified as serovar autumnalis by an agglutination test with immune rabbit sera. 相似文献
79.
Cardiac ICa is primarily controlled by the Ca2+ influx across the cell membrane during the action potential. Neurotransmitters and hormones are known to play an important role in controlling the availability of cardiac Ca2+ slow channels and [Ca]i through the transmembrane signaling systems, such as the receptor-adenylate cyclase system and the PI hydrolysis system. This article has reviewed some of the important properties of the transmembrane signaling systems for the control of Ca2+ channels and how they changed during development, especially in the rat heart. Since the phosphorylation hypothesis was first proposed over 15 years ago, considerable advances have been made in understanding the mechanisms for regulation of Ca2+ slow channels at the molecular level. During development, the properties of the cardiac Ca2+ channels, as well as the transmembrane signaling systems, change electrophysiologically, pharmacologically, and biochemically. Because conflicting data have been reported on the developmental changes in these properties, it is still not clear how the complex physiological function of the Ca2+ channels is gradually integrated during development. To answer this question, more data, new concepts, and new approaches are required. 相似文献
80.