全文获取类型
收费全文 | 1630篇 |
免费 | 227篇 |
国内免费 | 2篇 |
出版年
2022年 | 14篇 |
2021年 | 26篇 |
2020年 | 22篇 |
2019年 | 18篇 |
2018年 | 35篇 |
2017年 | 23篇 |
2016年 | 49篇 |
2015年 | 65篇 |
2014年 | 79篇 |
2013年 | 99篇 |
2012年 | 124篇 |
2011年 | 112篇 |
2010年 | 94篇 |
2009年 | 74篇 |
2008年 | 69篇 |
2007年 | 60篇 |
2006年 | 64篇 |
2005年 | 69篇 |
2004年 | 58篇 |
2003年 | 54篇 |
2002年 | 50篇 |
2001年 | 57篇 |
2000年 | 53篇 |
1999年 | 36篇 |
1998年 | 26篇 |
1997年 | 17篇 |
1996年 | 13篇 |
1995年 | 16篇 |
1994年 | 13篇 |
1993年 | 16篇 |
1992年 | 23篇 |
1991年 | 23篇 |
1990年 | 25篇 |
1989年 | 16篇 |
1988年 | 24篇 |
1987年 | 16篇 |
1986年 | 20篇 |
1985年 | 19篇 |
1984年 | 18篇 |
1983年 | 18篇 |
1982年 | 19篇 |
1980年 | 7篇 |
1979年 | 10篇 |
1978年 | 18篇 |
1977年 | 9篇 |
1976年 | 11篇 |
1974年 | 12篇 |
1972年 | 11篇 |
1971年 | 7篇 |
1968年 | 6篇 |
排序方式: 共有1859条查询结果,搜索用时 15 毫秒
1.
Hsuan-Hwai Lin Yi-Jen Peng Ming-Jiun Tsai Yi-Ying Wu Tsung-Neng Tsai Hsin-Hung Huang Yu-Lueng Shih Wei-Kuo Chang Tsai-Yuan Hsieh 《Journal of cellular physiology》2020,235(2):1689-1699
Activated hepatic stellate cells promote hepatocellular carcinoma (HCC) progression. Hepatic stellate cells play a key role in retinoid metabolism, and activation of stellate cells increases retinoic acid (RA) in the liver. However, the role of RA in HCC proliferation remains unclear. We aimed to analyse the mechanism of RA in HCC proliferation. Thirty-eight patients who had undergone hepatic resection for HCCs were recruited. Paired non-tumour tissues, adjacent and distal to HCCs, were collected, and the RA levels in the tissues were analysed. The mechanisms of RA and HCC proliferation were assessed in liver cancer cell lines by protein and gene expression analyses. Early recurrence of HCC was significantly higher in patients with a higher RA concentration than in those with a lower RA concentration in tissues adjacent to HCCs (61.1% vs. 20%, p = .010). RA promoted HCC cell proliferation and activated the expression of Amphiregulin, a growth factor in hepatocarcinogenesis. The promoter of Amphiregulin contained the binding sites of the RA receptor, RXRα. Wnt signalling also activated the expression of Amphiregulin, and the RA and Wnt pathways acted synergistically to increase the expression of Amphiregulin. Furthermore, RXRα interacted with β-catenin and then translocated to the nucleus to activate Amphiregulin. An increased RA concentration in the tissues adjacent to the tumour was associated with an early recurrence of HCC. RA activated the expression of Amphiregulin, and then promoted HCC proliferation, which might partly contribute to early recurrence of HCC after hepatic resection. 相似文献
2.
Dar-Fu Tai Ching-Chong Huang Hui-Yao Huang Ing-Lung Shih 《Biotechnology letters》1993,15(12):1229-1232
Summary Enzymatic hydrolysis of racemic 3-acetylthio-2-methylpropionic methyl ester catalyzed by bovine pancreatic protease and Mucor javanicus lipase showed opposite enantioselecivity. A tandem hydrolysis of the ester catalyzed by these two enzymes gives enantiomerically enriched (S)-3-acetylthio-2-methylpropionic acid, a building block of captopril. 相似文献
3.
Kuo Huang Ling Bai Jiun Chen Yun Wen Peng Shih Chong Tsai Fu Chuo Peng Chung Kuang Yang 《Mycotoxin Research》1987,3(2):58-64
The chemical reaction of cleavaging territrem B to give 3,4,5-trimethoxy benzoic acid by alkaline hydrogen peroxide was investigated. The method was applied for confirmation of the chemical structure of the aromatic moiety of territrem A, A’, B, and B’. The physicochemical properties of the aromatic cleavage product of territrem Aindicated the structure as 3,4-methylendioxy, 5-methoxy benzoic acid (or 4-methoxy, 6-carboxy, 1, 3-benzodioxole). The experiment also gave the evidences that territrem A and A’, on the other hand territrem B and B’ have the identical aromatic moieties on their structures. 相似文献
4.
C S Lai J Joseph C C Shih 《Biochemical and biophysical research communications》1989,160(3):1189-1195
We have synthesized a spin-labeled derivative of ET-18-OCH3, a known antitumor ether-linked phospholipid. The spin-labeled analog was shown to be as potent as ET-18-OCH3 in inhibiting 3H-thymidine uptake of HL60 leukemic cells. Electron spin resonance (ESR) studies showed that the mobility of this ether-linked phospholipid in the membrane is more restricted when compared to its ester-linked counterparts. It is probable that the absence of the bulky carbonyl oxygens allows closer packing of the two alkyl chains in the ether-linked phospholipid, thereby reducing the angular amplitude of the motion of the alkyl chains. These findings may be of importance in elucidating mechanisms by which the antitumor ether-linked phospholipids perturb the structure of cellular membranes. 相似文献
5.
Summary Methotrexate (MTX) was conjugated to an anti-carcinoembryonic antigen monoclonal antibody (NP2) by using amino-dextran as an intermediate carrier. The drug was chemically linked to amino-dextran (averageM
r = 40000), and the resulting MTX-dextran was then site-specifically attached to the carbohydrate moiety of the antibody. Athymic nude mice that carried human colonic GW-39 tumors (s. c.) were treated with the immunoconjugate. In this study, the specific conjugate caused a greater inhibition of the tumor growth than either free MTX or its conjugate with dextran and an irrelevant antibody. The intermediate MTX-dextran and the unlinked mixture of MTX-dextran with NP2 were both relatively ineffective in inhibiting tumor growth. The greatly reduced host toxicity permitted the use of the MTX-dextran-NP2 in a high-dose therapy of this tumor system.Supported in part by U.S.P.H.S. grant CA39 841 from the NIH 相似文献
6.
7.
Molybdenum cofactor deficiency in a patient previously characterized as deficient in sulfite oxidase 总被引:1,自引:0,他引:1
J L Johnson M M Wuebbens R Mandell V E Shih 《Biochemical medicine and metabolic biology》1988,40(1):86-93
The metabolic status of a patient previously characterized as deficient in sulfite oxidase was reexamined applying new methodology which has been developed to distinguish between a defect specific to the sulfite oxidase protein and sulfite oxidase deficiency which arises as a result of molybdenum cofactor deficiency. Urothione, the metabolic degradation product of the molybdenum cofactor, was undetectable in urine samples from the patient. Analysis of molybdenum cofactor levels in fibroblasts by monitoring reconstitution of apo nitrate reductase in extracts of the Neurospora crassa mutant nit-1 revealed that cells from the patient were severely depleted. Quantitation of urinary oxypurines showed that hypoxanthine and xanthine were highly elevated while uric acid remained in the normal range. These results were interpreted to indicate a severe but incomplete deficiency of the molybdenum cofactor. The presence of very low levels of active cofactor, supporting the synthesis of low levels of active sulfite oxidase and xanthine dehydrogenase, could explain the metabolic patterns of sulfur and purine products and the relatively mild clinical symptoms in this individual. 相似文献
8.
9.
Studies on the arrangement of glucocorticoid receptors in the plasma membrane of S-49 lymphoma cells. 总被引:1,自引:0,他引:1
The presence of glucocorticoid receptors is required for glucocorticoid-mediated lymphocytolysis to take place. However, the explicit mechanism of involvement of this receptor continues to be debated. We have recently presented evidence that this response is mediated by a specialized form of the glucocorticoid receptor that resides in the plasma membrane (mGR). Using sequential cell separation techniques ("immunopanning," fluorescent cell sorting, and soft agar cloning), a resultant population of membrane receptor-enriched cells have remained stable and provided material for further analysis. The mGR patching and capping phenomenon originally observed with fluoresceinated monoclonal antibody techniques was verified here with electron micrographic analysis using colloidal gold-conjugated antibody. Using 3H-labeled monoclonal antibody, a radioimmunoassay for membrane receptors was developed. Trypsin treatment removed the membrane receptor antigenic site from the surface of cells. Peptide mapping of receptor purified from plasma membranes reveals several trypsin and alpha-chymotrypsin cleavage sites. Larger fragments resulted from cleavage of the membrane receptor of cells enriched for mGR versus those found in cells depleted of the membrane form, although most of the resulting fragments are shared by the two forms. Confirmation of previous studies correlating membrane receptor with the mechanism of glucocorticoid sensitivity is now extended to include elimination of the lymphocytolysis effect in membrane receptor-stripped (trypsinized) S-49 cells. 相似文献
10.
Pyridoxine effects on ornithine ketoacid transaminase activity in fibroblasts from carriers of two forms of gyrate atrophy of the choroid and retina. 下载免费PDF全文
Gyrate atrophy of the choroid and retina that is due to ornithine ketoacid transaminase (OKT) deficiency is an autosomal recessive disorder. Fibroblasts from heterozygotes for the pyridoxine-responsive variant as well as those for the pyridoxine-nonresponsive variant contain intermediate levels of OKT activity. These two variants can be distinguished by the in vitro responsiveness of OKT activity to pyridoxal phosphate (PLP) stimulation. The ratios of OKT activity at 0.04 mM PLP compared with activity at 0 mM PLP were, respectively, lowest for controls (1.18 +/- 0.18; N = 12), intermediate for pyridoxine-nonresponsive heterozygotes (1.43 +/- 0.26; N = 5), and highest for pyridoxine-responsive heterozygotes (2.20 +/- 0.14; N = 3). 相似文献