全文获取类型
收费全文 | 308篇 |
免费 | 18篇 |
国内免费 | 3篇 |
专业分类
329篇 |
出版年
2019年 | 3篇 |
2017年 | 4篇 |
2016年 | 4篇 |
2015年 | 17篇 |
2014年 | 13篇 |
2013年 | 20篇 |
2012年 | 19篇 |
2011年 | 17篇 |
2010年 | 15篇 |
2009年 | 8篇 |
2008年 | 7篇 |
2007年 | 11篇 |
2006年 | 9篇 |
2005年 | 13篇 |
2004年 | 6篇 |
2003年 | 10篇 |
2002年 | 9篇 |
2001年 | 6篇 |
2000年 | 8篇 |
1999年 | 8篇 |
1998年 | 11篇 |
1997年 | 5篇 |
1996年 | 3篇 |
1995年 | 4篇 |
1994年 | 3篇 |
1993年 | 4篇 |
1992年 | 4篇 |
1991年 | 6篇 |
1990年 | 6篇 |
1989年 | 5篇 |
1988年 | 6篇 |
1987年 | 11篇 |
1986年 | 6篇 |
1985年 | 6篇 |
1983年 | 2篇 |
1982年 | 4篇 |
1981年 | 4篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1976年 | 1篇 |
1975年 | 4篇 |
1974年 | 6篇 |
1973年 | 1篇 |
1972年 | 3篇 |
1971年 | 1篇 |
1969年 | 3篇 |
1968年 | 2篇 |
1966年 | 1篇 |
1963年 | 1篇 |
1953年 | 1篇 |
排序方式: 共有329条查询结果,搜索用时 0 毫秒
82.
Formation of native insulin from the scrambled molecule by protein disulphide-isomerase. 总被引:5,自引:1,他引:4 下载免费PDF全文
The formation of native insulin either from scrambled insulin or from the separated A chain and B chain S-sulphonates by protein disulphide-isomerase was demonstrated with yields of 20-30% as measured by h.p.l.c. analysis, receptor binding and stimulation of lipogenesis. The h.p.l.c. profile of the reaction products shows that, among all the possible isomers containing both chains, the native hormone is by far the predominating product and consequently the most stable under certain conditions. 相似文献
83.
The presence of reactive SH groups in the enzymatically active dicyano derivative of creatine kinase 总被引:2,自引:0,他引:2
It has been shown that the active dicyano derivative of creatine kinase (ATP:creatine N-phosphotransferase) obtained by cyanolysis of the 5,5'-dithiobis(2-nitrobenzoic acid)-modified and inactivated enzyme contains, as does the native enzyme, two reactive SH groups. Modification of these two SH groups leads to complete inactivation of the dicyano enzyme. Reaction with 4-iodoacetamido-1-naphthol introduces fluorescent labels at these reactive SH groups of the native and the dicyano enzymes. Following tryptic digestion, the respective fluorescent-labelled peptides have been separated by HPLC and the amino acid composition analysis of these peptides has shown that they are consistent with the sequence of the peptide segment containing the active-site SH of Cys-282 of creatine kinase for both the native and the dicyano enzymes, showing that the active SH groups are free in the dicyano enzyme. Upon mild denaturation in 3 M urea, it can be shown that two of the SH groups partially buried in the native enzyme have been cyanylated in the dicyano enzyme. The two reactive SH groups are therefore essential for the activity of creatine kinase and the two cyanylated SH groups are internal groups which probably contributes partially to the stabilization of an active conformation of the enzyme molecule. 相似文献
84.
Activation of distinct protein kinase C isozymes by phorbol esters: correlation with induction of interleukin 1 beta gene expression 总被引:4,自引:0,他引:4
Treatment of human promyelocytic leukemia cells U937 with phorbol 12-myristate 13-acetate (TPA) induces them to differentiate into monocytic cells [Harris, P., & Ralph, P. (1985) J. Leukocyte Biol. 37, 407-422]. Here we investigated the effects of TPA on interleukin 1 gene expression and the possible role of protein kinase C (PKC) in this process. Addition of TPA to serum-starved U937 cells induced the expression of the interleukin 1 beta (IL-1 beta) gene. This effect was apparent as early as 2 h and peaked at 24 h in the presence of 5 X 10(-8) M TPA. Higher concentrations of TPA, which partially or totally depleted protein kinase C levels in the cells (10(-9)-2 X 10(-5) M), had an inhibitory effect on IL-1 beta mRNA expression. Cell-permeable 1,2-dioctanoyl-sn-glycerol (diC8), a diacylglycerol that activates PKC in intact cells and cell-free systems, did not mimic the effect of TPA on the IL-1 beta mRNA induction. To determine the protein kinase C isozymes present in the control and TPA- (5 X 10(-8) M) treated U937 cells, we prepared antipeptide antibodies that specifically recognize the alpha, beta, and gamma isoforms of protein kinase C in rat brain cytosol and U937 cell extracts. In "control" U937 cells, 30% of PKC alpha was particulate, and PKC beta was cytosolic, while there was no detectable PKC gamma.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
85.
Chung-Chih Tseng Chen-Han Tsou Shi-Ying Huang Chia-Wei Wu Tsung-Hua Hsieh 《Current issues in molecular biology》2022,44(5):2243
Oral squamous cell carcinoma (OSCC) is one of the most common cancers in the world, and the incidence and death rate of OSCC in men is twice that of women. CD47 is a ubiquitous cell surface transmembrane protein, also known as integrin-related protein (IAP). Previous studies have pointed out that CD47 can inhibit the growth of OSCC, but the detailed mechanism is not clear. This study aimed to explore the effect of CD47 gene expression profiles in OSCC. The OSCC cell lines, OECM-1 and OC-2, overexpressed CD47, and the expression profiles of mRNAs were analyzed through next-generation sequencing (NGS) with a bioinformatic approach. A total of 14 differentially expressed genes (DEGs) were listed. In addition, ingenuity pathway analysis (IPA) was used to analyze the molecular function (MF), biological process (BP), and cellular component (CC) network signaling. The human protein atlas (HPA) database was used to analyze gene expression and the survivability of human cancer. The results found that HSPA5, HYOU1, and PDIA4 were involved in the IPA network and when highly expressed, mediated the survivability of cancer. In addition, HSPA5 was positively and significantly correlated with CD47 expression (p < 0.0001) and induced by CD47-overexpression in the OECM-1 and OC-2 OSCC cancer cell lines. These findings provide important insights into possible new diagnostic strategies, including unfolded protein for OSCC-targeting CD47. 相似文献
86.
A perturbation of zinc metabolism has been noted in subjects with obesity. Zinc may also participate in the intracellular
signal cascade by affecting cellular calcium influx and a change in the calcium-calmodulin (CaM)-cyclic adenosine monophosphate
(cAMP) pathway. The possible effects of zinc on cellular concentrations of CaM, a major cytosolic calcium-binding protein,
in the adipocytes derived from obese (ob/ob) mice and their lean counterparts were studied. Adipocytes derived from both phenotypes
of mice were treated either with 0.2 mM of zinc sulfate or without any additive for 1 h of incubation; the cellular levels of CaM and cAMP were then determined.
The results showed that the obese mice had lower CaM and cAMP levels in their adipocytes compared to the lean mice. Zinc treatment
reduced CaM and increased cAMP levels in all mice, although this effect was more pronounced in the lean mice. This study indicated
that there was an inverse interaction between CaM and cAMP in their cellular levels in the mouse adipocytes and that might
be affected by exogenous zinc addition. 相似文献
87.
Hwei-Ru Tsou Gloria MacEwan Gary Birnberg Nan Zhang Natasja Brooijmans Lourdes Toral-Barza Irwin Hollander Semiramis Ayral-Kaloustian Ker Yu 《Bioorganic & medicinal chemistry letters》2010,20(7):2259-2263
A series of 5-ureidobenzofuranones was discovered as potent and selective inhibitors of mTOR with good cellular activity. Molecular modeling studies revealed several hydrogen bond interactions of the ureido group with the enzyme at the ATP-binding site. Furthermore, modeling showed that the ureido group is best situated at C-5 of the benzofuranone. Syntheses of 4-ureido and 5-ureidobenzofuranones are presented. 相似文献
88.
A genic male sterile Chinese cabbage, Brassica campestris L. ssp. chinensis Makino, was examined using cytological and cytochemical methods to characterize the process of pollen abortion in this plant.
Thick sections of both fertile and sterile anthers at different developmental stages were stained using Toluidine Blue O,
Periodic Acid-Schiff’s (PAS) reaction and Sudan Black B to detect cytochemical changes that may occur in the distribution
of insoluble polysaccharide and lipid storage bodies. Pollen abortion in sterile anthers occurs at an early stage of microspore
development. During early microspore development, reductions in the number of starch grains in the connective tissue of fertile
anthers coincide with the accumulation of starch grains in cells of the anther wall. In the late microspore stage, a large
vacuole forms in the microspore, and tapetal cells synthesize and accumulate lipid droplets. The cellular organization of
tapetal cells in sterile anthers appears similar to that in fertile anthers, except for the absence of lipid droplets in cells
of sterile anthers and diffusely labeled tapetal polysaccharides, suggesting defects in nutrient storage.
Supported by National Natural Science Foundation of CHINA (30170060) 相似文献
89.
Miao S Bao J Garcia ML Goulet JL Hong XJ Kaczorowski GJ Kayser F Koo GC Kotliar A Schmalhofer WA Shah K Sinclair PJ Slaughter RS Springer MS Staruch MJ Tsou NN Wong F Parsons WH Rupprecht KM 《Bioorganic & medicinal chemistry letters》2003,13(6):1161-1164
The voltage-gated potassium channel, Kv1.3, is present in human T-lymphocytes. Blockade of Kv1.3 results in T-cell depolarization, inhibition of T-cell activation, and attenuation of immune responses in vivo. A class of benzamide Kv1.3 channel inhibitors has been identified. The structure-activity relationship within this class of compounds in two functional assays, Rb_Kv and T-cell proliferation, is presented. In in vitro assays, trans isomers display moderate selectivity for binding to Kv1.3 over other Kv1.x channels present in human brain. 相似文献
90.
Accumulation of substrates by mitochondria 总被引:7,自引:0,他引:7