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21.
We have previously reported that Tamarix gallica caused a marked inhibition of thioacetamide-induced hepatotoxicity, oxidative damage and early tumor promotion related events in the liver. These results strongly indicates that T. gallica may have chemopreventive potential. Therefore, in the present study, we examined the inhibitory effects of T. gallica methanolic extract on diethylnitrosamine (DEN) initiated and 2-acetyl aminofluorene (2-AAF) promoted liver carcinogenesis in male Wistar rats. Interestingly, it was found that T. gallica (25 and 50 mg/kg body wt.) resulted in a marked reduction of the incidence of liver tumors. The study was further histologically confirmed. Furthermore to understand the underlying mechanisms of chemopreventive action by T. gallica we evaluated the levels activities of hepatic antioxidant defense enzymes, ornithine decarboxylase activity and hepatic DNA synthesis as a marker for tumor promotion since direct correlation between these marker parameters and carcinogenicity have been well documented. Treatment of male Wistar rats for five consecutive days with 2-AAF i.p. induced significant hepatic toxicity, oxidative stress and hyperproliferation. Pretreatment of T. gallica extract (25 and 50 mg/kg body wt.) prevented oxidative stress by restoring the levels of antioxidant enzymes and also prevented toxicity at both the doses. The promotion parameters induced (ornithine decarboxylase activity and DNA synthesis) by 2-AAF administration in diet with partial hepatectomy (PH) were also significantly suppressed dose-dependently by T. gallica. Therefore, we can conclude that ultimately the protection against liver carcinogenesis by T. gallica methanolic extract might be mediated by multiple actions, which include restoration of cellular antioxidant enzymes, detoxifying enzymes, ODC activity and DNA synthesis. 相似文献
22.
Sehrawat B Sridharan M Ghosh S Robson P Cass CE Mackey JR Greiner R Damaraju S 《Human genetics》2011,130(4):529-537
Previous genome-wide association studies (GWAS) have shown several risk alleles to be associated with breast cancer. However,
the variants identified so far contribute to only a small proportion of disease risk. The objective of our GWAS was to identify
additional novel breast cancer susceptibility variants and to replicate these findings in an independent cohort. We performed
a two-stage association study in a cohort of 3,064 women from Alberta, Canada. In Stage I, we interrogated 906,600 single
nucleotide polymorphisms (SNPs) on Affymetrix SNP 6.0 arrays using 348 breast cancer cases and 348 controls. We used single-locus
association tests to determine statistical significance for the observed differences in allele frequencies between cases and
controls. In Stage II, we attempted to replicate 35 significant markers identified in Stage I in an independent study of 1,153
cases and 1,215 controls. Genotyping of Stage II samples was done using Sequenom Mass-ARRAY iPlex platform. Six loci from
four different gene regions (chromosomes 4, 5, 16 and 19) showed statistically significant differences between cases and controls
in both Stage I and Stage II testing, and also in joint analysis. The identified variants were from EDNRA, ROPN1L, C16orf61 and ZNF577 gene regions. The presented joint analyses from the two-stage study design were not significant after genome-wide correction. The SNPs
identified in this study may serve as potential candidate loci for breast cancer risk in a further replication study in Stage
III from Alberta population or independent validation in Caucasian cohorts elsewhere. 相似文献
23.
Reddy PB Sehrawat S Suryawanshi A Rajasagi NK Mulik S Hirashima M Rouse BT 《Journal of immunology (Baltimore, Md. : 1950)》2011,187(11):5745-5755
After HSV-1 infection, CD8(+) T cells accumulate in the trigeminal ganglion (TG) and participate in the maintenance of latency. However, the mechanisms underlying intermittent virus reactivation are poorly understood. In this study, we demonstrate the role of an inhibitory interaction between T cell Ig and mucin domain-containing molecule 3 (Tim-3)-expressing CD8(+) T cells and galectin 9 (Gal-9) that could influence HSV-1 latency and reactivation. Accordingly, we show that most K(b)-gB tetramer-specific CD8(+) T cells in the TG of HSV-1-infected mice express Tim-3, a molecule that delivers negative signals to CD8(+) T cells upon engagement of its ligand Gal-9. Gal-9 was also upregulated in the TG when replicating virus was present as well during latency. This could set the stage for Gal-9/Tim-3 interaction, and this inhibitory interaction was responsible for reduced CD8(+) T cell effector function in wild-type mice. Additionally, TG cell cultures exposed to recombinant Gal-9 in the latent phase caused apoptosis of most CD8(+) T cells. Furthermore, Gal-9 knockout TG cultures showed delayed and reduced viral reactivation as compared with wild-type cultures, demonstrating the greater efficiency of CD8(+) T cells to inhibit virus reactivation in the absence of Gal-9. Moreover, the addition of recombinant Gal-9 to ex vivo TG cultures induced enhanced viral reactivation compared with untreated controls. Our results demonstrate that the host homeostatic mechanism mediated by Gal-9/Tim-3 interaction on CD8(+) T cells can influence the outcome of HSV-1 latent infection, and manipulating Gal-9 signals might represent therapeutic means to inhibit HSV-1 reactivation from latency. 相似文献
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26.
Vijeta Sharma Nagarjuna Amarnath Swapnil Shukla R. Ayana Naveen Kumar Nisha Yadav Deepika Kannan Seema Sehrawat Soumya Pati Bimlesh Lochab Shailja Singh 《Bioorganic & medicinal chemistry letters》2018,28(9):1629-1637
Development of new class of anti-malarial drugs is an essential requirement for the elimination of malaria. Bioactive components present in medicinal plants and their chemically modified derivatives could be a way forward towards the discovery of effective anti-malarial drugs. Herein, we describe a new class of compounds, 1,3-benzoxazine derivatives of pharmacologically active phytophenols eugenol (compound 3) and isoeugenol (compound 4) synthesised on the principles of green chemistry, as anti-malarials. Compound 4, showed highest anti-malarial activity with no cytotoxicity towards mammalian cells. Compound 4 induced alterations in the intracellular Na+ levels and mitochondrial depolarisation in intraerythrocytic Plasmodium falciparum leading to cell death. Knowing P-type cation ATPase PfATP4 is a regulator for sodium homeostasis, binding of compound 3, compound 4 and eugenol to PfATP4 was analysed by molecular docking studies. Compounds showed binding to the catalytic pocket of PfATP4, however compound 4 showed stronger binding due to the presence of propylene functionality, which corroborates its higher anti-malarial activity. Furthermore, anti-malarial half maximal effective concentration of compound 4 was reduced to 490?nM from 17.54?µM with nanomaterial graphene oxide. Altogether, this study presents anti-plasmodial potential of benzoxazine derivatives of phytophenols and establishes disruption of parasite sodium homeostasis as their mechanism of action. 相似文献
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28.
Retinopathy of prematurity (ROP) is a vasoproliferative disorder that occurs in premature infants and may lead to permanent visual impairment. We investigated both the possible protective role of N-acetyl cysteine (NAC) for preventing ROP and the role of IGF-1 in the disorder. Forty-five newborn rats were divided into three groups. Group 1 was raised in room air as controls. Group 2 was exposed to 60% oxygen for 14 days after birth, then transferred to room air. Group 3 was exposed to the same conditions as group 2, but received intraperitoneal injections of NAC on postnatal days 7–17. After 35 days, both eyes of all rats were processed for histology. Some sections were stained with hematoxylin and eosin to assess structural changes and other sections were immunostained to determine the location of IGF-1. Frozen sections also were prepared and stained for adenosine triphosphatase to detect retinal blood vessels. Compared to the controls, more blood vessels, many of which were abnormal, and increased IGF-1 expression were observed in group 2. In group 3, abnormal blood vessels and IGF-1 expression were less evident. NAC appeared to be an effective vascular-protective agent for ROP by decreasing IGF-1 expression. 相似文献
29.
Conserved sequences in enzymes of the UDP-GlcNAc/MurNAc family are essential in hamster UDP-GlcNAc:dolichol-P GlcNAc-1-P transferase 总被引:1,自引:0,他引:1
The UDP-GlcNAc/MurNAc family of eukaryotic and prokaryotic enzymes use
UDP-GlcNAc or UDP-MurNAc-pentapeptide as donors, dolichol-P or polyprenol-P
as acceptors, and generate sugar-P-P-polyisoprenols. A series of six
conserved sequences, designated A through F and ranging from 5 to 13 amino
acid residues, has been identified in this family. To determine whether
these conserved sequences are required for enzyme function, various
mutations were examined in hamster UDP- GlcNAc:dolichol-P GlcNAc-1-P
transferase (GPT). Scramble mutations of sequences B-F, generated by
scrambling the residues within each sequence, demonstrated that each is
important in GPT. While E and F scrambles appeared to prevent stable
expression of GPT, scrambling of B- D resulted in GPT mutants that could be
stably expressed and bound tunicamycin, but lacked enzymatic activity.
Further, the C and D scramble mutants had an unexpected sorting defect.
Replacement of sequences B-F with prokaryotic counterparts from either the
B.subtilis mraY or E.coli rfe genes also affected GPT by preventing
expression of the mutant protein (B, F) or inhibiting its enzymatic
activity (C-E). For the C-E replacements, no acquisition of acceptor
activity for polyprenol-P, the fully unsaturated natural bacterial
acceptor, was detected. These studies show that the conserved sequences of
the UDP- GlcNAc/MurNAc family are important, and that the eukaryotic and
prokaryotic counterparts are not freely interchangeable. Since several
mutants were efficiently expressed and bound tunicamycin, yet lacked
enzymatic activity, the data are consistent with these sequences having a
direct role in product formation.
相似文献
30.
JB Parentes-Vieira PV Lopes-Costa CG Pires AR dos Santos JD Pereira-Filho BB da Silva 《International Seminars in Surgical Oncology : ISSO》2007,4(1):22