全文获取类型
收费全文 | 496篇 |
免费 | 22篇 |
专业分类
518篇 |
出版年
2021年 | 3篇 |
2018年 | 5篇 |
2015年 | 12篇 |
2014年 | 6篇 |
2013年 | 26篇 |
2012年 | 24篇 |
2011年 | 16篇 |
2010年 | 15篇 |
2009年 | 14篇 |
2008年 | 28篇 |
2007年 | 15篇 |
2006年 | 19篇 |
2005年 | 24篇 |
2004年 | 13篇 |
2003年 | 8篇 |
2002年 | 21篇 |
2001年 | 16篇 |
2000年 | 24篇 |
1999年 | 14篇 |
1998年 | 5篇 |
1996年 | 3篇 |
1995年 | 9篇 |
1994年 | 3篇 |
1993年 | 6篇 |
1992年 | 18篇 |
1991年 | 12篇 |
1990年 | 11篇 |
1989年 | 9篇 |
1988年 | 10篇 |
1987年 | 8篇 |
1986年 | 6篇 |
1985年 | 9篇 |
1984年 | 4篇 |
1983年 | 4篇 |
1982年 | 8篇 |
1981年 | 5篇 |
1980年 | 3篇 |
1979年 | 7篇 |
1978年 | 8篇 |
1977年 | 8篇 |
1976年 | 10篇 |
1975年 | 6篇 |
1974年 | 3篇 |
1973年 | 6篇 |
1972年 | 2篇 |
1971年 | 5篇 |
1970年 | 9篇 |
1969年 | 3篇 |
1966年 | 3篇 |
1960年 | 2篇 |
排序方式: 共有518条查询结果,搜索用时 15 毫秒
31.
Mizuno K Tagawa Y Mitomo K Arimura Y Hatano N Katagiri T Ogimoto M Yakura H 《Journal of immunology (Baltimore, Md. : 1950)》2000,165(3):1344-1351
Src homology region 2 (SH2) domain-containing phosphatase-1 (SHP-1) is a cytosolic protein tyrosine phosphatase containing two SH2 domains in its NH2 terminus. That immunological abnormalities of the motheaten and viable motheaten mice are caused by mutations in the gene encoding SHP-1 indicates that SHP-1 plays important roles in lymphocyte differentiation, proliferation, and activation. To elucidate molecular mechanisms by which SHP-1 regulates BCR-mediated signal transduction, we determined SHP-1 substrates in B cells using the substrate-trapping approach. When the phosphatase activity-deficient form of SHP-1, in which the catalytic center cysteine (C453) was replaced with serine (SHP-1-C/S), was introduced in WEHI-231 cells, tyrosine phosphorylation of a protein of about 70 kDa was strongly enhanced. Immunoprecipitation and Western blot analyses revealed that this protein is the B cell linker protein (BLNK), also named SH2 domain leukocyte protein of 65 kDa, and that upon tyrosine phosphorylation BLNK binds to SHP-1-C/S in vitro. In vitro kinase assays demonstrated that hyperphosphorylation of BLNK in SHP-1-C/S-expressing cells was not due to enhanced activity of Lyn or Syk. Furthermore, BCR-induced activation of c-Jun NH2-terminal kinase was shown to be significantly enhanced in SHP-1-C/S transfectants. Taken collectively, our results suggest that BLNK is a physiological substrate of SHP-1 in B cells and that SHP-1 selectively regulates c-Jun NH2-terminal kinase activation. 相似文献
32.
Marine sediments from a Japanese bay were examined for the occurrence of Bacillus thuringiensis. Of 1313 colonies belonging to the Bacillus cereus/B. thuringiensis group, 22 (1.7%) were allocated to B. thuringiensis. Marine isolates of B. thuringiensis consisted of heterogeneous multiple H serogroups; 10 isolates were assigned to the eight serovars (kurstaki, sumiyoshiensis, sotto, aizawai, darmstadiensis, thompsoni, neoleonensis, and higo); two motile isolates failed to react with the reference antisera; and the others were serologically untestable. Insecticidal
activities were associated with two kurstaki isolates (toxic to both Lepidoptera and Diptera) and a higo isolate (Diptera-specific). None of the parasporal inclusion proteins of the 22 isolates exhibited in vitro cytotoxic activity
against two vertebrate cells, sheep erythrocytes and HeLa cells. All B. thuringiensis isolates had no halophilism, although seawater-based medium supported their growth, sporulation, and formation of parasporal
inclusions.
Received: 29 November 1999 / Accepted: 10 January 2000 相似文献
33.
Maruyama H Hatano H Kumagai T El-Malky M Yoshida A Ohta N 《Experimental parasitology》2000,95(3):170-175
Immunologically damaged Strongyloides venezuelensis adult worms were examined for their mucosal invasion ability and secretion of heparin-binding adhesion substances. S. venezuelensis was expelled from male Wistar rats 4 to 5 weeks after infection. Four-week-old adult worms were smaller and had fewer eggs than 1-week-old adult worms. One-week-old, 4-week-old, and 5-week-old adult worms equally established in the recipient mouse intestine when surgically implanted. Adult worms of 4 and 5 weeks of age secreted adhesion substances as much as 1-week-old adult worms. There was no difference in the heparin-binding activities and the lectin-binding profile of adhesion substances among adult worms of different ages. The rate of secretion of adhesion substances from the mouth was also identical. Heparin-binding activities were detected in crude adult worm proteins; however, proteins of 5-week-old adult worms had weaker heparin-binding activities than those of 1-week-old adult worms. Western blotting revealed that a number of heparin-binding proteins were lost in 5-week-old adult worms. A heparin-binding protein of 42. 0 kDa, which was consistently expressed in adult worms, was a possible component of heparin-binding adhesion substances which are secreted from the mouth. 相似文献
34.
The progressive oxidative transformations in the biogenesis of hydrolyzable tannins, gallotannin (I) --> ellagitannin (II) --> dehydro ellagitannin (III) --> transformed dehydroellagitannin (IV), conform in several aspects to the evolutionary routes in the subclasses of Dicotyledonae, particularly in the Rosidae. 相似文献
35.
400 MHz 1H NMR of ferric low-spin cytochrome P-450scc purified from bovine adrenal cortex was measured for the first time. As compared with 1H NMR spectra of low-spin P-450cam and metMb- mercaptan complexes, paramagnetic shifts of low-spin P-450scc complexes were more divergent, suggesting that there is a subtle difference in the heme environment between P-450scc and P-450cam [1]. The paramagnetic shifts of low-spin complexes of P-450scc caused by adding nitrogenous inhibitors, aminoglutethimide and metyrapone, were different from those caused by adding an intermediate, 20α-hydroxycholesterol, and a detergent, Tween 20 [2]. The paramagnetic shifts of the metMb-mercaptan complexes were convergent compared with those of ferric low-spin P-450scc and P-450cam, suggesting that the electronic character and/or the conformation of the internal thiolate ligand in P-450scc and P-450cam are different from those of the external thiolate ligand in metMb-thiolate complexes [3]. The paramagetic shifts of the metMb-mercaptan complexes were dependent on the electron donating factor of the alkyl group of the bound mercaptans [4].Magnetic CD(MCD) spectra of ferric low-spin P-450scc, rabbit liver P-450 complexes and metMb- mercaptan complexes were also observed at various temperatures. The temperature dependences of the Soret MCD bands for the low-spin P-450 and metMb- mercaptan complexes were decidedly less pronounced than those for the low-spin metMb-CN? or imidazole complexes, suggesting that thiolate ligands markedly influence the Soret MCD band of the ferric low-spin complexes [1]. The suggestion described in [2] implied by the 1H NMR study was reconfirmed from the temperature dependence study of the Soret MCD [2]. The temperature dependences of the Soret MCD bands for low-spin P-450 complexes having a non-nitrogenous ligand were more pronounced than for those having a nitrogenous ligand. 相似文献
36.
37.
Periostin is a secreted protein that shares a structural homology to the axon guidance protein fasciclin I (FAS1) in insects and was originally named as osteoblast-specific factor-2 (Osf2). Periostin is particularly highly homologus to Betaig-h3, which promotes cell adhesion and spreading of fibroblasts. It has recently been reported that Periostin was frequently overexpressed in various types of human cancers. Although the detailed function of Periostin is still unclear, Periostin-integrin interaction through FAS1 domain is thought to be involved in tumor development. In addition, Periostin stimulates metastatic growth by promoting cancer cell survival, invasion and angiogenesis. Therefore, Periostin can be a useful marker to predict the behavior of cancer. This review summarizes the recent understanding of Periostin roles in tumor development and speculates on the usefulness of Periostin as a therapeutic and diagnostic target for cancer. 相似文献
38.
Song T Sugimoto K Ihara H Mizutani A Hatano N Kume K Kambe T Yamaguchi F Tokuda M Watanabe Y 《The Biochemical journal》2007,401(2):391-398
Evidence is presented that RSK1 (ribosomal S6 kinase 1), a downstream target of MAPK (mitogen-activated protein kinase), directly phosphorylates nNOS (neuronal nitric oxide synthase) on Ser847 in response to mitogens. The phosphorylation thus increases greatly following EGF (epidermal growth factor) treatment of rat pituitary tumour GH3 cells and is reduced by exposure to the MEK (MAPK/extracellular-signal-regulated kinase kinase) inhibitor PD98059. Furthermore, it is significantly enhanced by expression of wild-type RSK1 and antagonized by kinase-inactive RSK1 or specific reduction of endogenous RSK1. EGF treatment of HEK-293 (human embryonic kidney) cells, expressing RSK1 and nNOS, led to inhibition of NOS enzyme activity, associated with an increase in phosphorylation of nNOS at Ser847, as is also the case in an in vitro assay. In addition, these phenomena were significantly blocked by treatment with the RSK inhibitor Ro31-8220. Cells expressing mutant nNOS (S847A) proved resistant to phosphorylation and decrease of NOS activity. Within minutes of adding EGF to transfected cells, RSK1 associated with nNOS and subsequently dissociated following more prolonged agonist stimulation. EGF-induced formation of the nNOS-RSK1 complex was significantly decreased by PD98059 treatment. Treatment with EGF further revealed phosphorylation of nNOS on Ser847 in rat hippocampal neurons and cerebellar granule cells. This EGF-induced phosphorylation was partially blocked by PD98059 and Ro31-8220. Together, these data provide substantial evidence that RSK1 associates with and phosphorylates nNOS on Ser847 following mitogen stimulation and suggest a novel role for RSK1 in the regulation of nitric oxide function in brain. 相似文献
39.
Ishimoto H Shibata M Myojin Y Ito H Sugimoto Y Tai A Hatano T 《Bioorganic & medicinal chemistry letters》2011,21(19):5901-5904
Urolithin A is a major metabolite produced by rats and humans after consumption of pomegranate juice or pure ellagitannin geraniin. In this study, we investigated the anti-inflammatory effect of urolithin A on carrageenan-induced paw edema in mice. The volume of paw edema was reduced at 1h after oral administration of urolithin A. In addition, plasma in treated mice exhibited significant oxygen radical antioxidant capacity (ORAC) scores with high plasma levels of the unconjugated form at 1h after oral administration of urolithin A. These results indicate strong associations among plasma urolithin A levels, the plasma ORAC scores, and anti-inflammatory effects and may help explain a mechanism by which ellagitannins confer protection against inflammatory diseases. 相似文献
40.
Specific effect of Ca2+ on movement of plasmodial fragment obtained by caffeine treatment 总被引:8,自引:0,他引:8
S Hatano 《Experimental cell research》1970,61(1):199-203