全文获取类型
收费全文 | 366篇 |
免费 | 21篇 |
专业分类
387篇 |
出版年
2023年 | 3篇 |
2022年 | 1篇 |
2021年 | 4篇 |
2020年 | 1篇 |
2019年 | 2篇 |
2018年 | 3篇 |
2017年 | 3篇 |
2016年 | 1篇 |
2015年 | 9篇 |
2014年 | 11篇 |
2013年 | 17篇 |
2012年 | 17篇 |
2011年 | 20篇 |
2010年 | 16篇 |
2009年 | 13篇 |
2008年 | 12篇 |
2007年 | 15篇 |
2006年 | 15篇 |
2005年 | 22篇 |
2004年 | 25篇 |
2003年 | 24篇 |
2002年 | 25篇 |
2001年 | 13篇 |
2000年 | 10篇 |
1999年 | 13篇 |
1998年 | 2篇 |
1997年 | 6篇 |
1996年 | 4篇 |
1995年 | 5篇 |
1994年 | 4篇 |
1993年 | 5篇 |
1992年 | 8篇 |
1991年 | 4篇 |
1990年 | 6篇 |
1989年 | 4篇 |
1988年 | 2篇 |
1987年 | 5篇 |
1986年 | 1篇 |
1985年 | 3篇 |
1984年 | 7篇 |
1983年 | 1篇 |
1982年 | 4篇 |
1981年 | 4篇 |
1980年 | 3篇 |
1979年 | 1篇 |
1978年 | 3篇 |
1977年 | 3篇 |
1976年 | 2篇 |
1975年 | 3篇 |
1973年 | 2篇 |
排序方式: 共有387条查询结果,搜索用时 15 毫秒
21.
Hori H Nagasawa H Ishibashi M Uto Y Hirata A Saijo K Ohkura K Kirk KL Uehara Y 《Bioorganic & medicinal chemistry》2002,10(10):3257-3265
A series of 2-hydroxyarylidene-4-cyclopentene-1,3-diones were designed, synthesized, and evaluated with respect to protein tyrosine kinase (PTK) inhibition, mitochondrial toxicity, and antitumor activity. Our results show that the cyclopentenedione-derived TX-1123 is a more potent antitumor tyrphostin and also shows lower mitochondrial toxicity than the malononitrile-derived AG17, a potent antitumor tyrphostin. The O-methylation product of TX-1123 (TX-1925) retained its tyrphostin-like properties, including mitochondrial toxicity and antitumor activities. However, the methylation product of AG17 (TX-1927) retained its tyrphostin-like antitumor activities, but lost its mitochondrial toxicity. Our comprehensive evaluation of these agents with respect to protein tyrosine kinase inhibition, mitochondrial inhibition, antitumor activity, and hepatotoxicity demonstrates that PTK inhibitors TX-1123 and TX-1925 are more promising candidates for antitumor agents than tyrphostin AG17. 相似文献
22.
Ohkura K Lee JD Shimizu H Nakano A Uzui H Horikoshi M Fujibayashi Y Yonekura Y Ueda T 《Molecular and cellular biochemistry》2003,248(1-2):203-208
We previously reported on the use of enzymatic analysis to impair fatty acid metabolism followed by reduced myocardial energy content, leading to severe heart failure in adriamycin (ADR)-treated rats. The aim of this study is to investigate whether impaired myocardial energy metabolism can also be detected by other methods; i.e. measuring mitochondrial complex I activity and myocardial 125I-15-(p-iodophenyl)-3-(R,S)- methylpentadecanoic acid (BMIPP) accumulation in ADR-treated rats. Eight-week-old male Sprague-Dawley rats received 6 intraperitoneal injections of ADR (total 15 mg/kg: group ADR) or saline (control group) over 2 weeks. Left ventricular (LV) ejection fraction was assessed using echocardiography at 3- and 6-weeks after ADR injection (3 weeks and 6 weeks, respectively). Myocardial fatty acid utilization was assessed at 3 weeks and 6 weeks. The myocardial counts of BMIPP were measured after intravenous BMIPP (370 kBq) injection, and 125I counts were measured to calculate the uptake ratio. The enzymatic activity of complex I was assessed by monitoring the oxidation of nicotinamide-adenine-dinucleotide-disodium-salt (NADH). In rats treated with ADR, significant decrease in LV ejection fraction was observed only at 6 weeks compared to control (72.5 vs. 84.5%, p < 0.01rpar;. LV ejection fraction at 3 weeks was identical between group ADR and control (81.8 vs. 84.4%). However, at 3 weeks, complex I activity was already reduced significantly in group ADR as compared to control group (p = 0.03), but the reduction in BMIPP accumulation was not (p = 0.15). Our data indicated that reduced complex I activity in a phenomenon occurred in early phase of ADR-induced cardiomyopathy, and it might play an important role in the progression of ADR-induced heart failure. 相似文献
23.
24.
Yamada K Tokunaga Y Ikeda A Ohkura K Kaku-Ohkura S Mamiya S Lim BO Tachibana H 《Bioscience, biotechnology, and biochemistry》2003,67(2):429-433
Eight-month-old Sprague-Dawley rats were fed on diets containing dietary fiber at the 5% level for 3 weeks to examine the effect on the lipid metabolism and immune function. Among cellulose, guar gum, partially hydrolyzed guar gum (PHGG), glucomannan and highly methoxylated pectin, guar gum induced a significant decrease in the food intake and weight gain, as well as a significant increase in the liver weight. In addition, the epidydimal adipose tissue weight of the rats fed on PHGG was significantly higher than that of the rats fed on cellulose. There was no significant effect on the serum lipid levels, but the serum IgG level of the rats fed on guar gum was significantly lower than that of the rats fed on cellulose. The IgA and IgG productivity in mesenteric lymph node (MLN) lymphocytes was significantly higher in the rats fed on guar gum, glucomannan and pectin than in those fed on cellulose, while the effect on Ig productivity in spleen lymphocytes was not as marked. In addition, only guar gum induced a significant increase of IgM productivity in MLN lymphocytes when compared to the cellulose group. These results suggest that enhancement of the immune function by dietary fiber is mainly expressed in the gut immune system. 相似文献
25.
26.
Three phospholipase A2 (PLA2) inhibitors (PLI) have been purified from the blood plasma of the Chinese mamushi, Agkistrodon blomhoffii siniticus; 1 of these, PLIgamma, contains 2 homologous subunits, PLIgamma-A and PLIgamma-B. The cDNAs encoding these 2 subunits of PLIgamma were isolated from a liver cDNA library by using fragments from polymerase chain reaction amplifications as probes and sequenced. The respective nucleotide sequences encoded 19-residue signal sequences, followed by 181-residue proteins. The calculated molecular masses were 20123 and 20150 Da for the PLIgamma-A and PLIgamma-B subunits, respectively; and PLIgamma-A included a N-linked carbohydrate site at Asn-157. The sequences of these subunits contained 2 internal repeats of disulfide-bonding pattern characteristic to those of urokinase-type plasminogen activator receptor and members of the Ly-6 superfamily. A phylogenetic analysis comparing the amino acid sequences of PLIgamma-A and PLIgamma-B with those for other snakes revealed that the gene duplication leading to these 2 subunits occurred before the divergence of Viperidae and Elapidae. 相似文献
27.
Expression profiles of fibrinolytic components in nasal mucosa 总被引:1,自引:1,他引:0
Sejima T Madoiwa S Mimuro J Sugo T Ishida T Ichimura K Sakata Y 《Histochemistry and cell biology》2004,122(1):61-73
28.
Nagamune H Ohkura K Sukeno A Cowan G Mitchell TJ Ito W Ohnishi O Hattori K Yamato M Hirota K Miyake Y Maeda T Kourai H 《Microbiology and immunology》2004,48(9):677-692
Intermedilysin is a pore-forming cytolysin belonging to the streptolysin O gene family known as the 'Cholesterol-binding/dependent cytolysins' and is unique within the family in that it is highly humanspecific. This specificity suggests interaction with a component of human cells other than cholesterol, the proposed receptor for the other toxins of the gene family. Indeed, intermedilysin showed no significant degree of affinity to free or liposome-embedded cholesterol. Characterization of intermedilysin undecapeptide mutants revealed that this lack of affinity to cholesterol was a result of the substitutions of intermedilysin in this region. Absorption assays with erythrocyte membranes from various animals, competitive inhibition with domain 4 of intermedilysin and liposome-binding assays of streptolysin O and intermedilysin indicated that cell membrane binding is the human-specific step of intermedilysin action, that the host cell membrane-binding site is located within domain 4 in common with other members of the family and that the receptor for this toxin is not cholesterol. The species specificity of undecapeptide mutants of intermedilysin and streptolysin O and chimeric mutants between intermedilysin and streptolysin O, and intermedilysin and pneumolysin indicated that domain 4 of intermedilysin determines the human-specific action step and the cell-binding site of domain 4 lies within the 56 amino acids of the C-terminal, excluding the undecapeptide region. 相似文献
29.
Ohkura H 《Current biology : CB》2003,13(23):R912-R914
30.
It has been proposed that the REV1 protein plays an important role in the induced-mutagenesis pathway. We show that purified REV1 protein inserts dCMP opposite template G, A, T and C, and dGMP and dTMP opposite template G in the presence of magnesium, while in the presence of manganese the specificity for dCMP was found to be relaxed and the REV1 protein acquired the ability to insert dCMP, dGMP, dAMP and dTMP opposite templates G, A, T, and C. Kinetic analysis provided evidence for high affinity for dCTP with template G, suggesting that the REV1 protein is specialized for dCTP and template G. 相似文献