全文获取类型
收费全文 | 1505篇 |
免费 | 137篇 |
国内免费 | 1篇 |
出版年
2021年 | 20篇 |
2020年 | 10篇 |
2019年 | 11篇 |
2018年 | 10篇 |
2017年 | 10篇 |
2016年 | 28篇 |
2015年 | 47篇 |
2014年 | 39篇 |
2013年 | 90篇 |
2012年 | 101篇 |
2011年 | 95篇 |
2010年 | 61篇 |
2009年 | 48篇 |
2008年 | 82篇 |
2007年 | 92篇 |
2006年 | 84篇 |
2005年 | 87篇 |
2004年 | 103篇 |
2003年 | 66篇 |
2002年 | 74篇 |
2001年 | 49篇 |
2000年 | 48篇 |
1999年 | 45篇 |
1998年 | 21篇 |
1997年 | 12篇 |
1996年 | 21篇 |
1995年 | 20篇 |
1994年 | 12篇 |
1993年 | 12篇 |
1992年 | 19篇 |
1991年 | 24篇 |
1990年 | 24篇 |
1989年 | 19篇 |
1988年 | 14篇 |
1987年 | 15篇 |
1986年 | 27篇 |
1985年 | 14篇 |
1984年 | 16篇 |
1983年 | 10篇 |
1982年 | 3篇 |
1981年 | 6篇 |
1980年 | 4篇 |
1979年 | 12篇 |
1978年 | 7篇 |
1977年 | 3篇 |
1976年 | 3篇 |
1975年 | 3篇 |
1972年 | 5篇 |
1968年 | 3篇 |
1967年 | 3篇 |
排序方式: 共有1643条查询结果,搜索用时 31 毫秒
31.
32.
33.
Identification of membrane anchoring site of human renal dipeptidase and construction and expression of a cDNA for its secretory form 总被引:1,自引:0,他引:1
H Adachi T Katayama C Inuzuka S Oikawa M Tsujimoto H Nakazato 《The Journal of biological chemistry》1990,265(25):15341-15345
The chemical properties of human renal dipeptidase (hrDP) purified from the membrane fraction of kidney have been characterized. When treated with phosphatidylinositol-specific phospholipase C, hrDP was released from renal membrane fractions. After digestion with trypsin, carboxyl-terminal peptide was isolated employing anhydrotrypsin-agarose column chromatography and reversed-phase high performance liquid chromatography. The amino acid sequence of the peptide was identified at positions 363-369 in the primary structure deduced from the cDNA sequence (Adachi, H., Tawaragi, Y., Inuzuka, C., Kubota, I., Tsujimoto, M., Nishihara, T., And Nakazato, H. (1990) J. Biol. Chem. 265, 3992-3995). Further examination of the chemical composion of the peptide showed that it contained, respectively, 2, 1, 5, 1, and 1 mol of ethanolamine, glucosamine, mannose, inositol, and phosphate in addition to amino acids. These results suggest that the mature hrDP molecule lacks the carboxyl-terminal hydrophobic peptide extension predicted from the cDNA sequence and is anchored at Ser369 via glycosylphosphatidylinositol to the membrane. To characterize further the action of the enzyme, we have established expression systems for both secretory and membrane anchored forms of hrDP using COS-1 cells and found that both recombinant forms were as active as natural enzyme. Our expression system made it possible to prepare large amounts of soluble enzyme, and will contribute toward elucidation of the physiological roles of the enzyme. 相似文献
34.
Effect of Dichloroacetate on Regional Energy Metabolites and Pyruvate Dehydrogenase Activity During Ischemia and Reperfusion in Gerbil Brain 总被引:1,自引:1,他引:0
The objective of this study was to determine whether administration of dichloroacetate (DCA), an activator of pyruvate dehydrogenase (PDH), improves recovery of energy metabolites following transient cerebral ischemia. Gerbils were pretreated with DCA, and cerebral ischemia was produced using bilateral carotid artery occlusion for 20 min, followed by reperfusion up to 4 h. DCA had no effect on the accumulation of lactic acid and the decrease in ATP and phosphocreatine (PCr) during the 20-min insult, nor on the recovery of these metabolites measured at 20 and 60 min reperfusion. However, at 4 h reperfusion, levels of ATP and PCr were significantly higher in DCA-treated animals than in controls, as PCr exhibited a secondary decrease in caudate nucleus of control animals. PDH was markedly inhibited at 20 min reperfusion in both groups, but was reactivated to a greater extent in DCA-treated animals at 60 min and 4 h reperfusion. These results demonstrate that DCA had no effect on the initial recovery of metabolites following transient ischemia. However, later in reperfusion, DCA enhanced the postischemic reactivation of PDH and prevented the secondary failure of energy metabolism in caudate nucleus. Thus, inhibition of PDH may limit the recovery of energy metabolism following cerebral ischemia. 相似文献
35.
K Ueno T Katayama T Miyamoto Y Koshihara 《Biochemical and biophysical research communications》1992,189(3):1521-1526
The effect of human interleukin-4 (hIL-4) on mineralization in human osteoblast-like cells was investigated. Confluent cells were incubated with hIL-4 for 16 or 30 days in the presence or absence, respectively, of alpha-glycerophosphate (alpha-GP), which accelerates the mineralization process. hIL-4 (0.3 ng/ml) induced mineralization with 1.9-, 26- and 37-fold increases of hydroxyproline, calcium, and osteocalcin content, respectively, in the presence of alpha-GP. Mineralization was not induced with other cytokines, hIL-1, hIL-2, hIL-6, or mIL-4. hIL-4 also induced mineralization in the absence of alpha-GP in a manner different from that of 1 alpha, 25(OH)2 vitaminD3 (1,25(OH)2VD3). These findings suggest that IL-4 may play an important role in bone formation. 相似文献
36.
Takashi Kamaishi Tetsuo Hashimoto Yoshihiro Nakamura Fuminori Nakamura Shigenori Murata Norihiro Okada Ken-ichi Okamoto Makoto Shimizu Masami Hasegawa 《Journal of molecular evolution》1996,42(2):257-263
Partial regions of the mRNA encoding a major part of translation elongation factor 1 (EF-1) from a mitochondrion-lacking protozoan,Glugea plecoglossi, that belongs to microsporidians, were amplified by polymerase chain reaction (PCR) and their primary structures were analyzed. The deduced amino acid sequence was highly divergent from typical EF-1's of eukaryotes, although it clearly showed a eukaryotic feature when aligned with homologs of the three primary kingdoms. Maximum likelihood (ML) analyses on the basis of six different stochastic models of amino acid substitutions and a maximum parsimony (MP) analysis consistently suggest that among eukaryotic species being analyzed,G. plecoglossi is likely to represent the earliest offshoot of eukaryotes. Microsporidians might be the extremely ancient eukaryotes which have diverged before an occurrence of mitochondrial symbiosis.
Sequence availability: The nucleotide sequence data reported here appear in the GSDB, DDBJ, EMBL, and NCBI databases with the accession number D32139 相似文献
37.
Hiroko Soda Shigenori Yukizane Ichiro Yoshida Yasutoshi Koga Shuichi Aramaki Hirohisa Kato 《Human genetics》1996,97(4):435-437
We have analyzed two unrelated Japanese patients with carbonic anhydrase II deficiency born to consanguineous parents. We
have identified the same mutation as that reported to be homozygous in a Belgian family and compound heterozygous in an American
family. It comprises to C-to-T transition that results in the amino acid substitution of Tyr (TAT) for His (CAT) at position
107. This point mutation creates an AccI site that can be conveniently screened by the polymerase chain reaction/restriction fragment length polymorphism method
using a restriction enzyme for gene tracking. Our patients exhibit severe mental retardation, not seen in the Belgian and
American patients.
Received: 23 November 1994 / Revised: 22 May 1995 相似文献
38.
Shigenori Goto Sumitaka Sakai Jiro Kera Yukie Suma Gen-Ichiro Soma Shoshichi Takeuchi 《Cancer immunology, immunotherapy : CII》1996,42(4):255-261
Lipopolysaccharide (LPS) has been recognized as a potent antitumor agent in animal tumor models; however, its use in human
cancer therapy has been limited to only one trial, in which LPS from Salmonella was given intravenously. It was not very successful because of poor tumor response and was also toxic. We originally developed
LPS prepared from Pantoea agglomerans (LPSp), and this was a well-purified, small-molecular-mass (5 kDa) agent. We chose intradermal rather than intravenous administration
in the hope that the former would release LPS slowly into the bloodstream, and thus be less toxic while preserving antitumor
activity. In our animal tumor models, intradermal administration was indeed less toxic and more beneficial for tumor regression
than intravenous administration. We made a pilot study with intradermal administration of LPSp on the treatment of ten advanced
cancer patients. Five of them had evaluable tumor, which had failed earlier to respond to conventional chemotherapy. Cyclophosphamide
was also administered in this trial, in anticipation of its synergistic effect with LPSp. In this study LPSp was injected
intradermally into each patient twice a week, starting with an initial dose of 0.4 ng/kg, and raising it to 600 or 1800 ng/kg.
A 400-mg/m2 dose of cyclophosphamide was given intravenously every 2 weeks. After completion of the dose escalation, the treatment was
continued for at least 4 months, and it was found that 1800 ng/kg LPSp was well tolerated. A significant level of cytokines
was observed in the sera for at least 8 h. These results indicate higher tolerable doses and remarkably more continuous induction
of the cytokines than were reported in a previous study by others using intravenous administration. Three of the five evaluable
tumors showed a significant response to our combined therapy. Intradermally administered, LPS was less toxic and elicited
a tumor response in combination with cyclophosphamide; it can thus can be applied to cancer treatment even in humans.
Received: 3 August 1995 / Accepted: 2 April 1996 相似文献
39.
Yuriko Osakabe Kazuya Nanto Hiroko Kitamura Shinya Kawai Yuki Kondo Tomoyuki Fujii Keiji Takabe Yoshihiro Katayama Noriyuki Morohoshi 《Planta》1996,200(1):13-19
The polypeptide encoded by the partial fragment of cDNA of phenylalanine ammonia-lyase (PAL; EC 4.3.1.5), PALcDNAl (Osakabe et al., 1995, Plant Sci. 105: 217–226), isolated from Populus kitakamiensis (P. sieboldii x P. grandidentata), was expressed in Escherichia coli cells. The polypeptide was purified and an antiserum raised against it. The antiserum recognized a protein of 77 kDa on nitrocellulose blots after sodium dodecyl sulfate-poly-acrylamide gel electrophoresis of total protein and the partially purified PAL protein from P. kitakamiensis. Moreover,the antiserum recognized a protein on the blot after non-denaturing polyacrylamide gel electrophoresis of P. kitakamiensis proteins and this protein had PAL activity. Furthermore, the antibody inhibited PAL activity of extracts from stem tissues. These results showed that the antiserum against the partial PAL peptide recognized only the PAL subunits in extracts of P. kitakamiensis. Immunolocalization studies of P. kitakamiensis tissues revealed that the PAL protein was specifically localized in the xylem and the phloem fibers and no immunogold signal was found in the epidermis, the cortex, the pith, or the cambium of either stems or leaves.Abbreviations IgG
immunoglobulin G
- IPTG
isopropylthio--d-galactoside
- PAL
phenylalanine ammonia-lyase
The authors thank Dr. Kunio Hata of Nippon Paper Industries Co., Ltd. (Japan) for supplying P. kitakamiensis. This work was supported in part by a grant-in-aid for Scientific Research from the Ministry of Education, Science and Culture of Japan (No. 07406008). 相似文献
40.
F. Morishita A. Shimada Y. Takeda M. Fujimoto H. Katayama K. Yamada 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》1996,166(8):467-472
To investigate the functions of GTP-binding protein(s) in the melanosome-aggregating response in fish melanophores, the effects
of activators of G-proteins, namely, mastoparan and compound 48/80, were examined in cultured melanophores of the balck-moor
goldfish, Carassius auratus. Both mastoparan and compound 48/80 induced an approximately 40% increase in the GTP-hydrolyzing activity in the melanophore
membranes compared to the basal level. In intact melanophores, these compounds inhibited the effect of 3-isobutyl-1-methylxanthine,
which induced the accumulation of intracellular cAMP. Pretreatment of melanophores with pertussis toxin at 1 μg ⋅ ml-1 for 15 h attenuated the inhibitory effect of mastoparan on the accumulation of cAMP. However, pretreatment with the toxin
only slightly attenuated the inhibitory effect of compound 48/80 on the accumulation of cAMP. In addition, compound 48/80
at 1 mg ⋅ ml-1 induced full aggregation of the melanosomes in melanophores, though mastoparan at 5 μmol ⋅ l-1 induced only 10–20% aggregation of melanophores. These results suggest that mastoparan and compound 48/80 can each activate
the inhibitory G-protein in goldfish melanophores, which results in inhibition of adenylate cyclase activity. This signal-transduction
pathway is involved in the aggregation of melanosomes in these cells.
Accepted: 3 June 1996 相似文献