全文获取类型
收费全文 | 433篇 |
免费 | 24篇 |
出版年
2023年 | 2篇 |
2022年 | 2篇 |
2021年 | 4篇 |
2020年 | 6篇 |
2019年 | 3篇 |
2018年 | 6篇 |
2017年 | 4篇 |
2015年 | 8篇 |
2014年 | 19篇 |
2013年 | 21篇 |
2012年 | 10篇 |
2011年 | 10篇 |
2010年 | 16篇 |
2009年 | 12篇 |
2008年 | 20篇 |
2007年 | 21篇 |
2006年 | 25篇 |
2005年 | 36篇 |
2004年 | 13篇 |
2003年 | 20篇 |
2002年 | 28篇 |
2001年 | 12篇 |
2000年 | 10篇 |
1999年 | 10篇 |
1998年 | 9篇 |
1997年 | 6篇 |
1996年 | 7篇 |
1995年 | 7篇 |
1994年 | 9篇 |
1993年 | 3篇 |
1992年 | 10篇 |
1991年 | 8篇 |
1990年 | 7篇 |
1989年 | 7篇 |
1988年 | 4篇 |
1987年 | 5篇 |
1986年 | 10篇 |
1985年 | 2篇 |
1984年 | 4篇 |
1983年 | 8篇 |
1981年 | 2篇 |
1979年 | 9篇 |
1978年 | 4篇 |
1977年 | 2篇 |
1976年 | 3篇 |
1975年 | 2篇 |
1974年 | 3篇 |
1970年 | 2篇 |
1969年 | 2篇 |
1968年 | 2篇 |
排序方式: 共有457条查询结果,搜索用时 93 毫秒
51.
We studied the synergistic effect of visible light and ferritin on the lipid peroxidation on a fraction of porcine photoreceptor outer segment (POS). Reaction mixtures containing the POS fraction and horse spleen ferritin were irradiated under white fluorescent light mainly at 17,000 lx or incubated under dark conditions at 37°C. The lipid peroxidation was evaluated by both the thiobarbituric acid method and the ferrous oxidation/xylenol orange method. The irradiation-induced lipid peroxidation was affected by some experimental factors such as the irradiation dose and acidity of the material. When the irradiation was stopped, the lipid peroxidation was also stopped; thereafter, the re-irradiation induced lipid peroxidation. Moreover, this lipid peroxidation was inhibited by desferrioxamine, an iron chelator, or by dimethylthiourea, a hydroxyl radical scavenger, suggesting that the lipid peroxidation involves hydroxyl radicals generated via the Fenton reaction by iron ion released from ferritin. The lipid peroxidation did not take place under dark conditions or in the absence of ferritin. This study suggested the possibility that the visible light-induced lipid peroxidation of the POS fraction in the presence of ferritin may participate in the etiology of human retinal degenerative diseases as the human retina is exposed to light for life. 相似文献
52.
ABSTRACT: BACKGROUND: Kleine-Levin syndrome is a rare idiopathic form of episodic hypersomnia that typically occurs during adolescence. The cardinal clinical features are recurrent hypersomnia, accompanied by cognitive disturbances and behavioral abnormalities [1]. The most typical form of classical Kleine-Levin syndrome is associated with hyperphagia [2, 3], although hyperphagia is now optional after change of the criteria. Hypersexuality, behavioral disinhibition, delusions, autonomic alteration and hallucinations have also been described, but the patients show normal cognitive function and behavior between attacks. The pathogenesis of Kleine-Levin syndrome is not yet known. Although most cases of recurrent hypersomnia are sporadic, the occurrence of nine familial cases indicate that there may be a genetic predisposition to the syndrome [4-8] However, no cases of twins affected with Kleine-Levin syndrome have been reported [9]. In this case study we describe monozygotic twins suffering from the syndrome. This is the first case report describing twins affected with Kleine-Levin syndrome thereby supporting the theory that there is an underlying genetic predisposition to the syndrome. 相似文献
53.
54.
55.
Placental hydroxysteroid 11-beta dehydrogenase 2 (HSD11B2) plays an important role in pregnancy maintenance and fetal maturation. In the event of intrauterine infection, lipoxygenase (LOX) metabolites are produced in the placenta and contribute to preterm labor and adverse fetal outcomes. On the other hand, LOX metabolites are involved in production of progesterone, which is required for pregnancy maintenance. In this study, we evaluated the interaction between the LOX pathway, progesterone, and HSD11B2. Specifically, we hypothesized that LOX metabolites would alter HSD11B2 and this effect would be mediated by progesterone. We cultured human term placental trophoblasts in the presence and absence of the LOX inhibitors Nordihydroguaiaretic acid (NDGA), AA861, and Baicalein; the LOX metabolites Leukotriene B(4) and 12(S)-Hydroxyeicosatetraenoate (12-HETE); and progesterone and progesterone receptor antagonist RU486. By radiometric conversion assay, real-time quantitative PCR, Western blot analysis, and ELISA, we examined HSD11B2 enzyme activity, HSD11B2 mRNA and HSD11B2 protein expression, and progesterone output. LOX metabolites down-regulated HSD11B2 activity and HSD11B2 expression. LOX inhibitors up-regulated HSD11B2 activity and HSD11B2 and HSD11B2 expression, and these effects were attenuated by addition of LOX metabolites. Net progesterone output was increased by LOX metabolites and decreased by LOX inhibitors. Progesterone down-regulated HSD11B2 activity and HSD11B2 and HSD11B2 expression, and these effects were blocked by RU486. Furthermore, the suppressive effect of 12-HETE on HSD11B2 activity was also reversed by RU486. We conclude that HSD11B2 in human placental trophoblasts is decreased by progesterone and increased by inhibition of endogenous LOX metabolites, and that a component of the effect of LOX metabolites on HSD11B2 is mediated by their stimulation of endogenous progesterone output. 相似文献
56.
Hojo H Igawa K Ohba S Yano F Nakajima K Komiyama Y Ikeda T Lichtler AC Woo JT Yonezawa T Takato T Chung UI 《Biochemical and biophysical research communications》2008,376(2):375-379
To effectively treat osteoporosis and other bone-loss disorders, small compounds that potently induce bone formation are needed. The present study initially attempted to establish a monitoring system that could detect osteogenic differentiation easily, precisely, and noninvasively. For this purpose, we established pre-osteoblastic MC3T3E1 cells stably transfected with the GFP reporter gene driven by a 2.3 kb fragment of rat type I collagen promoter (Col1a1GFP-MC3T3E1). Among these cells, we selected a clone that fluoresced upon osteogenic stimulation by BMP2. The GFP fluorescence intensity corresponded well to the intensity of alkaline phosphatase (ALP) staining and to the level of osteocalcin (Oc) mRNA. Using this system, we screened natural and synthetic compound libraries and thus identified an isoflavone derivative, glabrisoflavone (GI). GI induced ALP staining and Oc mRNA in a dose-dependent manner. The Col1a1GFP-MC3T3E1 system may be useful for identifying novel osteogenic drugs. 相似文献
57.
Research has shown that adults’ recognition of a facial part can be disrupted if the part is learnt without a face context but tested in a whole face. This has been interpreted as the holistic interference effect. The present study investigated whether children of 6- and 9–10-year-olds would show a similar effect. Participants were asked to judge whether a probe part was the same as or different from a test part whereby the part was presented either in isolation or in a whole face. The results showed that while all the groups were susceptible to a holistic interference, the youngest group was most severely affected. Contrary to the view that piecemeal processing precedes holistic processing in the cognitive development, our findings demonstrate that holistic processing is already present at 6 years of age. It is the ability to inhibit the influence of holistic information on piecemeal processing that seems to require a longer period of development into at an older and adult age. 相似文献
58.
Chie Amano Hideki Minematsu Kazuyo Fujita Shinki Iwashita Masaki Adachi Koichi Igarashi Shuji Hinuma 《PloS one》2015,10(9)
To explore a novel method using liposomes to suppress macrophages, we screened food constituents through cell culture assays. Curcumin was one of the strongest compounds exhibiting suppressive effects on macrophages. We subsequently tried various methods to prepare liposomal curcumin, and eventually succeeded in preparing liposomes with sufficient amounts of curcumin to suppress macrophages by incorporating a complex of curcumin and bovine serum albumin. The diameter of the resultant nanoparticles, the liposomes containing curcumin, ranged from 60 to 100 nm. Flow cytometric analyses revealed that after intraperitoneal administration of the liposomes containing curcumin into mice, these were incorporated mainly by macrophages positive for F4/80, CD36, and CD11b antigens. Peritoneal cells prepared from mice injected in vivo with the liposomes containing curcumin apparently decreased interleukin-6-producing activities. Major changes in body weight and survival rates in the mice were not observed after administrating the liposomes containing curcumin. These results indicate that the liposomes containing curcumin are safe and useful for the selective suppression of macrophages in vivo in mice. 相似文献
59.
M Minami Y Minami Y Emori H Kawasaki S Ohno K Suzuki N Ohishi T Shimizu Y Seyama 《FEBS letters》1988,229(2):279-282
The cDNA clone encoding human leukotriene A4 hydrolase was inserted into a vector pUC9 and expressed in Escherichia coli as a fusion protein containing the first 10 amino acid residues derived from a vector. The leukotriene A4 hydrolase activity was recovered in the soluble fraction of the transformants. The purified enzyme showed kinetic properties similar to the native enzyme, including inactivation by the substrate and sulfhydryl-modifying reagents. The results demonstrate that a protein with an Mr of 70,000 was expressed in Escherichia coli with a full enzyme activity and structural fidelity. Acquisition of the expression system makes it feasible to elucidate the reaction mechanism of the enzyme. 相似文献
60.
Y Hong K Ohishi R Watanabe Y Endo Y Maeda T Kinoshita 《The Journal of biological chemistry》1999,274(26):18582-18588
Attachment of glycosylphosphatidylinositol (GPI) is essential for the surface expression of many proteins. Biosynthesis of glycosylphosphatidylinositol is initiated by the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol. In mammalian cells, this reaction is mediated by a complex of PIG-A, PIG-H, PIG-C, and GPI1. This complexity may be relevant for regulation and for usage of a particular phosphatidylinositol. However, the functions of the respective components have been unclear. Here we cloned the mouse GPI1 gene and disrupted it in F9 embryonal carcinoma cells. Disruption of the GPI1 gene caused a severe but not complete defect in the generation of glycosylphosphatidylinositol-anchored proteins, indicating some residual biosynthetic activity. A complex of PIG-A, PIG-H, and PIG-C decreased to a nearly undetectable level, whereas a complex of PIG-A and PIG-H was easily detected. A lack of GPI1 also caused partial decreases of PIG-C and PIG-H. Therefore, GPI1 stabilizes the enzyme by tying up PIG-C with a complex of PIG-A and PIG-H. 相似文献