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111.
Srivastava Neelam Chowdhury Paritosh Roy Averna Maurizio Srivastava Rai Ajit K. 《Molecular and cellular biochemistry》2001,220(1-2):87-93
We have shown mouse to be an useful animal model for studies on the estrogen-mediated synthesis and secretion of lipoproteins since, unlike in rats, low density lipoprotein receptors are not upregulated in mice [3]. This results into the elevation of plasma levels of apolipoprotein (apo) B and apoE, and lowering of apoA-I-containing particles. The mechanisms of apoB and apoE elevation by estrogen have been elucidated [6], but the mechanism of lowering of plasma levels of HDL is still not known. Among other factors, apoA-I, cholesterol ester transfer protein (CETP), scavenger receptor B1 (SR-B1), and hepatic lipase are potential candidates that modulate plasma levels of HDL. Since estrogen treatment increased hepatic apoA-I mRNA and apoA-I synthesis, and mouse express undetectable levels of CETP, we tested the hypothesis that estradiol-mediated lowering of HDL in mice may occur through modulation of hepatic lipase (HL). Four mouse strains (C57L, C57BL, BALB, C3H) were administered supraphysiological doses of estradiol, and plasma levels of HDL as well as HL mRNA were quantitated. In all 4 strains estradiol decreased plasma levels of HDL by 30%, and increased HL mRNA 2–3 fold. In a separate experiment groups of male C57BL mouse were castrated or sham-operated, and low and high doses of estradiol administered. We found 1.4–2.5 fold elevation of HL mRNA with concomitant lowering of HDL levels. Ten other mouse strains examined also showed estradiol-induced elevation of HL mRNA, but the extent of elevation was found to be strain-specific. Based on these studies, we conclude that hepatic lipase is an important determinant of plasma levels of HDL and that HL mRNA is modulated by estrogen which in turn may participate in the lowering of plasma levels of HDL. 相似文献
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A novel microtubule depolymerizing colchicine analogue triggers apoptosis and autophagy in HCT‐116 colon cancer cells
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Ashok Kumar Baljinder Singh Parduman R. Sharma Sandip B. Bharate Ajit K. Saxena D. M. Mondhe 《Cell biochemistry and function》2016,34(2):69-81
Colchicine is a tubulin‐binding natural product isolated from Colchicum autumnale. Here we report the in vitro anticancer activity of C‐ring modified semi‐synthetic derivative of colchicine; N‐[(7S)‐1,2,3‐trimethoxy‐9‐oxo‐10‐(4‐phenyl‐piperidin‐1‐yl)‐5,6,7,9 tetrahydrobenzo[a]heptalen‐7‐yl]acetamide ( 4h ) on colon cancer HCT‐116 cell line. The compound 4h was screened for anti‐proliferative activity against different human cancer cell lines and was found to exhibit higher cytotoxicity against colon cancer cell lines HCT‐116 and Colo‐205 with IC50 of 1 and 0.8 μM respectively. Cytotoxicity of the compound to the normal fR2 breast epithelial cells and normal HEK293 human embryonic kidney cells was evaluated in concentration and time‐dependent manner to estimate its selectivity for cancer cells which showed much better selectivity than that of colchicine. Compound 4h induced cell death in HCT‐116 cells by activating apoptosis and autophagy pathways. Autophagy inhibitor 3‐MA blocked the production of LC3‐II and reduced the cytotoxicity in response to 4h , but did not affect apoptosis, suggesting thereby that these two were independent events. Reactive oxygen species scavenger ascorbic acid pretreatment not only decreased the reactive oxygen species level but also reversed 4h induced cytotoxicity. Treatment with compound 4h depolymerized microtubules and the majority of cells arrested at the G2/M transition. Together, these data suggest that 4h has better selectivity and is a microtubule depolymerizer, which activates dual cell‐death machineries, and thus, it could be a potential novel therapeutic agent in cancer therapy. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献
115.
Fig. 1. The sialic acids. The nine-carbon backbone common toall sialic acids is shown. Natural substitutions described todate (at C4, C5, C7 C8, and C9,) are indicated. Additional diversityis generated by various types of glycosidic linkage (at R3)by generation of lactones (at C1 ), by dehydro forms (eliminatingR3), and anhydro forms diversity sialic acids neuraminic acids O-acetylation sialidase 相似文献
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We report the occurrence of a freshwater medusa from a laboratory aquarium in Ranchi, Bihar, India. The consistent emergence of these medussae coincided with sunny days after heavy and prolonged rainfall in the months of August to October. The material showed similarity with Limnocnide indica Annandale and L. nepalensis Dumont but differed in many respects, and is given the status of a distinct species, Limnocnida biharensis n.sp.Author to whom all correspondence should be addressed.Author to whom all correspondence should be addressed. 相似文献
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Choon Young Lee Ajit Sharma Jae Eun Cheong Julie L. Nelson 《Bioorganic & medicinal chemistry letters》2009,19(22):215-6330
Three dendritic polyphenols (generation 1) were synthesized: a syringaldehyde-based dendrimer (1), a vanillin-based dendrimer (2), and an iodinated vanillin-based dendrimer (3). They all showed strong antioxidant activity according to the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical assay. The syringaldehyde dendrimer was twice and 10 times stronger than quercetin and Trolox, respectively. The vanillin-based dendrimer and its more hydrophobic iodinated derivative were also more potent antioxidants than quercetin and Trolox. The DPPH order of potency was 1 > 2, 3 > quercetin > Trolox. All three dendrimers also protected human LDL from free radical attack in a dose-dependent manner. Their order of free radical scavenging was 1 > 3 > 2 > quercetin > Trolox. The increased hydrophobic nature of the iodinated derivative may have contributed to its better LDL protection than 2. Protection of linoleic acid oxidation was studied by the β-carotene–linoleate assay. Dendrimer 1 was clearly superior to the other antioxidants in protecting the fatty acid. In case of DNA protection against free radical damage, the order of activity was 1 > quercetin > 2 > 3, Trolox. Pro-oxidant effect on copper-induced DNA oxidation showed the following order: quercetin, Trolox > 1 > 2 > 3. Results of the study show that dendritic antioxidants, even at the generation 1 level, provide promising antioxidant properties for their potential use as drug candidates for diseases associated with oxidative stress. 相似文献
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Kenyi Saito-Diaz Hassina Benchabane Ajit Tiwari Ai Tian Bin Li Joshua J. Thompson Annastasia S. Hyde Leah M. Sawyer Jeanne N. Jodoin Eduardo Santos Laura A. Lee Robert J. Coffey R. Daniel Beauchamp Christopher S. Williams Anne K. Kenworthy David J. Robbins Yashi Ahmed Ethan Lee 《Developmental cell》2018,44(5):566-581.e8