全文获取类型
收费全文 | 3625篇 |
免费 | 364篇 |
国内免费 | 1篇 |
出版年
2023年 | 36篇 |
2022年 | 105篇 |
2021年 | 172篇 |
2020年 | 77篇 |
2019年 | 92篇 |
2018年 | 95篇 |
2017年 | 83篇 |
2016年 | 143篇 |
2015年 | 218篇 |
2014年 | 215篇 |
2013年 | 224篇 |
2012年 | 290篇 |
2011年 | 251篇 |
2010年 | 160篇 |
2009年 | 144篇 |
2008年 | 198篇 |
2007年 | 167篇 |
2006年 | 163篇 |
2005年 | 151篇 |
2004年 | 138篇 |
2003年 | 106篇 |
2002年 | 113篇 |
2001年 | 63篇 |
2000年 | 75篇 |
1999年 | 51篇 |
1998年 | 37篇 |
1997年 | 21篇 |
1996年 | 20篇 |
1995年 | 17篇 |
1994年 | 26篇 |
1993年 | 13篇 |
1992年 | 33篇 |
1991年 | 33篇 |
1990年 | 25篇 |
1989年 | 26篇 |
1988年 | 24篇 |
1987年 | 20篇 |
1986年 | 16篇 |
1985年 | 8篇 |
1984年 | 5篇 |
1983年 | 6篇 |
1981年 | 8篇 |
1980年 | 9篇 |
1979年 | 8篇 |
1978年 | 9篇 |
1977年 | 9篇 |
1976年 | 8篇 |
1975年 | 6篇 |
1974年 | 6篇 |
1955年 | 4篇 |
排序方式: 共有3990条查询结果,搜索用时 15 毫秒
941.
Baek JY Han SH Sung SH Lee HE Kim YM Noh YH Bae SH Rhee SG Chang TS 《The Journal of biological chemistry》2012,287(1):81-89
Sulfiredoxin (Srx) is an enzyme that catalyzes the reduction of cysteine sulfinic acid of hyperoxidized peroxiredoxins (Prxs). Having high affinity toward H2O2, 2-Cys Prxs can efficiently reduce H2O2 at low concentration. We previously showed that Prx I is hyperoxidized at a rate of 0.072% per turnover even in the presence of low steady-state levels of H2O2. Here we examine the novel role of Srx in cells exposed to low steady-state levels of H2O2, which can be achieved by using glucose oxidase. Exposure of low steady-state levels of H2O2 (10-20 μm) to A549 or wild-type mouse embryonic fibroblast (MEF) cells does not lead to any significant change in oxidative injury because of the maintenance of balance between H2O2 production and elimination. In contrast, loss-of-function studies using Srx-depleted A549 and Srx-/- MEF cells demonstrate a dramatic increase in extra- and intracellular H2O2, sulfinic 2-Cys Prxs, and apoptosis. Concomitant with hyperoxidation of mitochondrial Prx III, Srx-depleted cells show an activation of mitochondria-mediated apoptotic pathways including mitochondria membrane potential collapse, cytochrome c release, and caspase activation. Furthermore, adenoviral re-expression of Srx in Srx-depleted A549 or Srx-/- MEF cells promotes the reactivation of sulfinic 2-Cys Prxs and results in cellular resistance to apoptosis, with enhanced removal of H2O2. These results indicate that Srx functions as a novel component to maintain the balance between H2O2 production and elimination and then protects cells from apoptosis even in the presence of low steady-state levels of H2O2. 相似文献
942.
Osei-Owusu P Sabharwal R Kaltenbronn KM Rhee MH Chapleau MW Dietrich HH Blumer KJ 《The Journal of biological chemistry》2012,287(15):12541-12549
Regulator of G protein signaling 2 (RGS2) is a GTPase-activating protein for G(q/11)α and G(i/o)α subunits. RGS2 deficiency is linked to hypertension in mice and humans, although causative mechanisms are not understood. Because endothelial dysfunction and increased peripheral resistance are hallmarks of hypertension, determining whether RGS2 regulates microvascular reactivity may reveal mechanisms relevant to cardiovascular disease. Here we have determined the effects of systemic versus endothelium- or vascular smooth muscle-specific deletion of RGS2 on microvascular contraction and relaxation. Contraction and relaxation of mesenteric resistance arteries were analyzed in response to phenylephrine, sodium nitroprusside, or acetylcholine with or without inhibitors of nitric oxide (NO) synthase or K(+) channels that mediate endothelium-derived hyperpolarizing factor (EDHF)-dependent relaxation. The results showed that deleting RGS2 in vascular smooth muscle had minor effects. Systemic or endothelium-specific deletion of RGS2 strikingly inhibited acetylcholine-evoked relaxation. Endothelium-specific deletion of RGS2 had little effect on NO-dependent relaxation but markedly impaired EDHF-dependent relaxation. Acute, inducible deletion of RGS2 in endothelium did not affect blood pressure significantly. Impaired EDHF-mediated vasodilatation was rescued by blocking G(i/o)α activation with pertussis toxin. These findings indicated that systemic or endothelium-specific RGS2 deficiency causes endothelial dysfunction resulting in impaired EDHF-dependent vasodilatation. RGS2 deficiency enables endothelial G(i/o) activity to inhibit EDHF-dependent relaxation, whereas RGS2 sufficiency facilitates EDHF-evoked relaxation by squelching endothelial G(i/o) activity. Mutation or down-regulation of RGS2 in hypertension patients therefore may contribute to endothelial dysfunction and defective EDHF-dependent relaxation. Blunting G(i/o) signaling might improve endothelial function in such patients. 相似文献
943.
944.
Two perchlorate-reducing bacterial consortia (PRBC) were obtained by enrichment cultures from polluted marine sediments. Non-salt-tolerant PRBC (N-PRBC) was enriched without the addition of NaCl, and salt tolerant-PRBC (ST-PRBC) was enriched with 30 g-NaCl L−1. Although the perchlorate reduction rates decreased with increasing NaCl concentration, ST-PRBC (resp., N-PRBC) could reduce perchlorate until 75 g-NaCl L−1 (resp., 30 g-NaCl L−1). The reduction yield (1.34 ± 0.05 mg-perchlorate per mg-acetate) and maximum perchlorate reduction rate (86 mg-perchlorate L−1 h−1) of ST-PRBC was higher than those (1.16 ± 0.03 mg-perchlorate per mg-acetate and 48 mg-perchlorate L−1 h−1) of N-PRBC. Kinetic analysis showed that NaCl acted as an uncompetitive inhibitor against both PRBCs. The inhibition constants were 25 and 41 mg-NaCl L−1 for N-PRBC and ST-PRBC, respectively. 相似文献
945.
Dakin LA Block MH Chen H Code E Dowling JE Feng X Ferguson AD Green I Hird AW Howard T Keeton EK Lamb ML Lyne PD Pollard H Read J Wu AJ Zhang T Zheng X 《Bioorganic & medicinal chemistry letters》2012,22(14):4599-4604
Novel substituted benzylidene-1,3-thiazolidine-2,4-diones (TZDs) have been identified as potent and highly selective inhibitors of the PIM kinases. The synthesis and SAR of these compounds are described, along with X-ray crystallographic, anti-proliferative, and selectivity data. 相似文献
946.
MB Donald KX Rodriguez H Shay PW Phuan AS Verkman MJ Kurth 《Bioorganic & medicinal chemistry》2012,20(17):5247-5253
Copper catalyzed azide-alkyne cycloaddition (CuAAC) chemistry is reported for the construction of previously unknown 5-(1H-1,2,3-triazol-1-yl)-4,5'-bithiazoles from 2-bromo-1-(thiazol-5-yl)ethanones. These novel triazolobithiazoles are shown to have cystic fibrosis (CF) corrector activity and, compared to the benchmark bithiazole CF corrector corr-4a, improved logP values (4.5 vs 5.96). 相似文献
947.
948.
949.
Methane emissions have been previously detected from orangutans, but characterization of the diversity of methanogens in this species has yet to be completed. This preliminary study identified methanogen producing microorganims, also called methanogens, present in the feces from a colony of captive Sumatran orangutans at the Perth Zoo. All animals were housed in the same enclosure and were fed primarily a frugivorous diet. Methanogens were detected using a 16S rRNA gene clone library. A total of 207 clones were examined, revealing 37 different methanogen 16S rRNA sequences, or phylotypes. Of these, 31 phylotypes represented by 170 clones had 96.4-100% sequence identity to Methanosphaera stadtmanae, four phylotypes (32 clones) had 95.1-100% sequence identity to Methanobrevibacter smithii, while two phylotypes (five clones) had 95.9-97.7% sequence identity to Methanobacterium beijingense. Overall, five possible new species were identified from the clone library. This represents the first report of Msp. stadtmanae, a methanol utilizer, as the most predominant methanogen in the gastrointestinal tract of animals. This is likely due to the increased availability of methanol from the highly frugivorous diet of the orangutans. Further studies are warranted to properly assess the effects of frugivorous diets on the methanogen population. 相似文献
950.
The (R)-specific enoyl-CoA hydratase gene (phaJ(HS21)) from Pseudomonas chlororaphis HS21 was overexpressed in various Pseudomonas strains, alone and in combination with the polyhydroxyalkanoate synthase gene (phaC(HS21)), for the biosynthesis of polyhydroxyalkanoates (PHAs) of altered monomer composition. Recombinant Pseudomonas strains harboring phaC(HS21) and phaJ(HS21) generated saturated and unsaturated monomers of C12-C14 in their PHAs. In particular, the level of the 3-hydroxytetradecenoate monomer in recombinant P. chlororaphis HS21 increased by approximately 260%. PhaJ(HS21) is expected to be useful in the biosynthesis of PHAs consisting of unusual monomer units. 相似文献