全文获取类型
收费全文 | 8094篇 |
免费 | 596篇 |
国内免费 | 1篇 |
出版年
2024年 | 5篇 |
2023年 | 31篇 |
2022年 | 76篇 |
2021年 | 166篇 |
2020年 | 136篇 |
2019年 | 161篇 |
2018年 | 238篇 |
2017年 | 183篇 |
2016年 | 318篇 |
2015年 | 469篇 |
2014年 | 563篇 |
2013年 | 623篇 |
2012年 | 771篇 |
2011年 | 698篇 |
2010年 | 501篇 |
2009年 | 421篇 |
2008年 | 585篇 |
2007年 | 514篇 |
2006年 | 468篇 |
2005年 | 384篇 |
2004年 | 422篇 |
2003年 | 322篇 |
2002年 | 269篇 |
2001年 | 59篇 |
2000年 | 46篇 |
1999年 | 46篇 |
1998年 | 62篇 |
1997年 | 30篇 |
1996年 | 22篇 |
1995年 | 20篇 |
1994年 | 12篇 |
1993年 | 9篇 |
1992年 | 7篇 |
1991年 | 4篇 |
1990年 | 9篇 |
1989年 | 4篇 |
1988年 | 6篇 |
1987年 | 4篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1979年 | 2篇 |
1974年 | 2篇 |
1970年 | 1篇 |
1968年 | 1篇 |
1967年 | 1篇 |
1965年 | 2篇 |
1963年 | 1篇 |
1962年 | 1篇 |
排序方式: 共有8691条查询结果,搜索用时 15 毫秒
991.
Kim DH Kim JM Lee EK Choi YJ Kim CH Choi JS Kim ND Yu BP Chung HY 《The Journal of nutritional biochemistry》2012,23(10):1277-1284
Baicalin is a flavonoid known to modify various redox-related biological activities. Included is its ability to suppress reactive species (RS) producing activity and modulate nuclear factor-κB through cellular redox regulation with enhanced thiol ability. FoxO regulates various genes that are known to be involved in cellular metabolism related to cell death and the oxidative stress response. One such case is the prevention of FoxO1 expression by activated insulin-induced phosphatidylinositol 3-kinase (PI3K)/Akt, which leads to increased oxidative stress and aging processes. In the present study, we attempted to elucidate the molecular modulation of antioxidant baicalin on the insulin-induced FoxO1 inactivation. We used HEK293T cultured cells and kidney tissue isolated from 24-month-old rats treated with baicalin at a dose of 10 or 20 mg/kg/day for 10 days. We found that baicalin enhanced catalase and suppressed RS production in cell system and in isolated kidney tissue in contrast to the nontreated aged rats. Results also showed activation of insulin signaling (PI3K/Akt), FoxO1 phosphorylation/acetylation and the down-regulation of catalase and manganese superoxide dismutase, both of which are FoxO1-targeting genes. Furthermore, baicalin-treated rats showed a decreased FoxO1 phosphorylation via PI3K/Akt cascade and FoxO1 acetylation by the cAMP-response element-binding protein binding protein (CBP). These results strongly suggest that treatment with baicalin influenced phosphorylation/acetylation of FoxO1 by up-regulating PI3K/Akt signaling through insulin in aged rats. Our results further reveal that baicalin regulated FoxO1 phosphorylation via PI3K/Akt by insulin and FoxO1 acetylation by the interaction of CBP and SIRT1, leading to changes in catalase gene expression during aging. 相似文献
992.
Kim YJ Houng SJ Kim JH Kim YR Ji HG Lee SJ 《The Journal of nutritional biochemistry》2012,23(2):186-191
Nanoemulsification of nutrients could improve bioavailability by enhancing intestinal uptake. We investigated the antioxidant and hypolipidemic effects of nanoemulsified green tea extract (NGTE). Antioxidant effect was measured by 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging assay and dichlorofluorescein diacetate (DCFH-DA) assay. C57BL/6 mice were fed a control high-fat diet, green tea extract (GTE), or NGTE diet for 4 weeks. In composition analysis, GTE and NGTE contained similar total catechin concentrations. The antioxidative effect of GTE was comparable with that of NGTE. In the ABTS assay, GTE had a marked effect, although NGTE was more effective than GTE in the DCFH-DA assay. In the mouse feeding experiment, total and low-density lipoprotein (LDL) cholesterol concentrations were significantly reduced after NGTE treatment in comparison with GTE treatment in high-fat-fed C57BL/6J mice over the course of 4 weeks. The hypocholesterolemic effects were greater in the NGTE group compared with the GTE group (24% vs. 15.4% LDL cholesterol reduction compared with the control). Expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase was significantly down-regulated. Protein expression of LDL receptor was significantly increased in the livers of both the GTE- and NGTE-treated groups (+234.1%, P<.01 and +274.7%, P<.001), with a greater effect in the NGTE than in the GTE group. Cholesterol 7α-hydroxylase gene expression was similarly increased in both the GTE and NGTE groups. These results suggest that nanoemulsification significantly increased hypocholesterolemic effects of GTE in vivo due to increased bioavailability. 相似文献
993.
Han SY Choi JW Yang J Chae CH Lee J Jung H Lee K Ha JD Kim HR Cho SY 《Bioorganic & medicinal chemistry letters》2012,22(8):2837-2842
A series of 3-(4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridin-2-yl)-1H-quinolin-2-ones have been identified as a new class of VEGFR-2 kinase inhibitors. A variety of (4,5,6,7-tetrahydro-imidazo[5,4-c]pyridin-2-yl)-acetic acid ethyl esters were synthesized, and their VEGFR-2 inhibitory activity was evaluated. Described herein are the preparation of the series and the effects of the compounds on VEGFR-2 kinase activity. 相似文献
994.
HJ Kim WY Kwak JP Min SY Sung HD Kim MK Kim HS Kim KJ Park MH Son SH Kim BJ Lee 《Bioorganic & medicinal chemistry letters》2012,22(17):5545-5549
Inhibitors of dipeptidyl peptidase-4 (DPP4) have been shown to be effective treatments for type 2 diabetes. Several series of β-amino amide containing piperazine derivatives have been prepared and evaluated as a inhibitor of DPP4. Finally compound 5m was selected for further evaluation. 相似文献
995.
996.
The ability to estimate binding affinities of ligands precisely is of paramount importance in designing drugs. Docking programs are used primarily to predict the binding mode of ligands to receptors. However, current scoring functions as used in docking programs are not reliable enough to predict binding affinities of ligands without any further calculations. In the present study, we investigate the usefulness of adding π-π interaction energies between ring groups of residues and ligands to the scoring function for docking. It is found that such addition helps ranking ligand activities more correctly. LMP2 calculation is used to measure π-π interaction energies between ring groups. The result of this simple addition shows possibility of π-π interaction generalization in scoring functions. 相似文献
997.
Kim YA Kong CS Lee JI Kim H Park HY Lee HS Lee C Seo Y 《Bioorganic & medicinal chemistry letters》2012,22(13):4318-4322
As a part of an ongoing search for novel antioxidants from the salt marsh plants, bioactivity-isolation and structure determination of constituents from Salicornia herbacea were performed. One new triterpenoid saponin (4), along with three known saponins (1-3), has been isolated from n-BuOH fraction of S. herbacea. On the basis of the spectroscopic methods, the structure of the new saponin 4 was elucidated as 3β-hydroxy-23-oxo-30-noroleana-12, 20(29)-diene-28-oic acid 3-O-β-D-glucuronopyranosyl-28-O-β-d-glucopyranoside. Scavenging effects of saponins 1-4 were examined on 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical and peroxynitrite. Particularly, saponin 3 exerted significant antioxidant activity on both authentic peroxynitrite and peroxynitrite generated from morpholinosydnonimine (SIN-1). 相似文献
998.
Seung Hyun Lee Young-Sun Lee In Yong Lee Jae Won Lim Hee-Kwan Shin Jae-Ran Yu Seobo Sim 《The Korean journal of parasitology》2012,50(4):327-331
Monthly surveys were conducted to investigate the occurrence of chigger mites and seroprevalence of scrub typhus among small mammals in Jeollanam-do, the southwestern part of Korea, from November 2006 through October 2007. Fifty-eight small mammals, including 57 Apodemus agrarius (98.3%) and 1 Crocidura lasiura (1.7%), were captured, and a total of 4,675 chigger mites representing 4 genera and 8 species were collected from them. The chigger infestation rate among small mammals was 69.0%. The most predominant species in A. agrarius was Leptotrombidium scutellare (54.0%), followed by Leptotrombidium pallidum (39.4%), Leptotrombidium orientale (4.4%), Leptotrombidium palpale (1.1%), Neotrombicula tamiyai (0.6%), Eushoengastia koreaensis (0.3%), Neotrombicula gardellai (0.3%), and Cheladonta ikaoensis (<0.1%). The chigger index of A. agrarius was the highest in October (740.0), followed by November (242.0), September (134.6), March (98.3), February (38.2), January (35.3), December (34.5), April (30.8), and May (1.7). The average antibody positive rate of scrub typhus in wild rodents was 50.0%. The seropositive rates were high in October (100.0%) and November (83.3%), whereas those in other months were relatively low (28.6-57.1%). The chigger index of L. scutellare rapidly increased in September to form an acuminate peak in October, followed by a gradual decline. These results suggest that the outbreak of scrub typhus in the southwestern part of Korean peninsula is mostly due to L. scutellare. 相似文献
999.
AimsThe expression of cell adhesion molecules on vascular smooth muscle cells is central to leukocyte recruitment and progression of atherosclerotic disease. Ohioensin F, a chemical compound of the Antarctic moss Polyerichastrum alpinum, exhibited inhibitory activity against protein tyrosine phosphatase 1B and antioxidant activity. However, published scientific information regarding other biological activities and pharmacological function of ohioensin F is scarce. In the present study, we aimed to examine the in vitro effects of ohioensin F on the ability to suppress TNF-α-induced adhesion molecule expression in vascular smooth muscle cells (VSMCs).Main methodsThe inhibitory effect of ohioensin F on TNF-α-induced upregulation in expression of adhesion molecules was investigated by enzyme-linked immunosorbent assay, cell adhesion assay, RT-PCR, western blot analysis, immunofluorescence, and transfection and reporter assay, respectively.Key findingsPretreatment of VSMCs with ohioensin F at nontoxic concentrations of 0.1–10 μg/ml dose-dependently inhibited TNF-α-induced expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). In addition, ohioensin F suppressed adhesion of THP-1 monocytes to TNF-α-stimulated VSMCs. Ohioensin F reduced TNF-α-induced production of intracellular reactive oxygen species (ROS) and phosphorylation of p38, ERK, JNK and Akt. Finally, ohioensin F inhibited TNF-α-induced CAM mRNA expression and NK-κB translocation.SignificanceThese results suggest a new mechanism of ohioensin F's anti-inflammatory action, owing to the negative regulation of TNF-α-induced adhesion molecule expression, monocyte adhesion and ROS production in vascular smooth muscle cells. Our finding also supports ohioensin F as a potential pharmacological, anti-inflammatory molecule that has a protective effect on the atherosclerotic lesion. 相似文献
1000.
Roles of four Arabidopsis u-box e3 ubiquitin ligases in negative regulation of abscisic Acid-mediated drought stress responses 总被引:1,自引:0,他引:1
DH Seo MY Ryu F Jammes JH Hwang M Turek BG Kang JM Kwak WT Kim 《Plant physiology》2012,160(1):556-568
AtPUB18 and AtPUB19 are homologous U-box E3 ubiquitin ligases in Arabidopsis (Arabidopsis thaliana). AtPUB19 is a negative regulator of abscisic acid (ABA)-mediated drought responses, whereas the role of AtPUB18 in drought responses is unknown. Here, loss-of-function and overexpression tests identified AtPUB18 as a negative regulator in ABA-mediated stomatal closure and water stress responses. The atpub18-2atpub19-3 double mutant line displayed more sensitivity to ABA and enhanced drought tolerance than each single mutant plant; therefore, AtPUB18 and AtPUB19 are agonistic. Stomatal closure of the atpub18-2atpub19-3 mutant was hypersensitive to hydrogen peroxide (H(2)O(2)) but not to calcium, suggesting that AtPUB18 and AtPUB19 exert negative effects on the ABA signaling pathway downstream of H(2)O(2) and upstream of calcium. AtPUB22 and AtPUB23 are other U-box E3 negative regulators of drought responses. Although atpub22atpub23 was more tolerant to drought stress relative to wild-type plants, its ABA-mediated stomatal movements were highly similar to those of wild-type plants. The atpub18-2atpub19-3atpub22atpub23 quadruple mutant exhibited enhanced tolerance to drought stress as compared with each atpub18-2atpub19-3 and atpub22atpub23 double mutant progeny; however, its stomatal behavior was almost identical to the atpub18-2atpub19-3 double mutant in the presence of ABA, H(2)O(2), and calcium. Overexpression of AtPUB18 and AtPUB19 in atpub22atpub23 effectively hindered ABA-dependent stomatal closure, but overexpression of AtPUB22 and AtPUB23 in atpub18-2atpub19-3 did not inhibit ABA-enhanced stomatal closure, highlighting their ABA-independent roles. Overall, these results suggest that AtPUB18 has a linked function with AtPUB19, but is independent from AtPUB22 and AtPUB23, in negative regulation of ABA-mediated drought stress responses. 相似文献