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121.
Ziolkowska A Rucinski M Pucher A Tortorella C Nussdorfer GG Malendowicz LK 《Chemico-biological interactions》2006,164(3):147-156
Compelling evidence indicates that some endocrine disrupters (EDs), acting as selective estrogen-receptor modulators, interfere with osteoblast differentiation and function. Hence, we investigated whether four EDs [bisphenol-A (BSP), benzophenone-3 (BP3), resveratrol and silymarin] affect differentiation and growth of rat calvarial osteoblast-like (ROB) cells in primary in vitro culture. ROB cells were cultured for up 30 days in a medium supplemented with fetal calf serum (FCS), and conventional RT-PCR detected the expression of collagen-1alpha and osteonectin mRNAs through the entire culture period. Real time-PCR demonstrated that at days 2 and 7 of culture the expressions of collagen-1alpha and osteonectin were very low, and underwent a 192- and a 334-fold increase, respectively, at day 21 of culture. In contrast, osteocalcin expression remained unchanged from days 2 to 21 of culture. EIA showed that ROB cells secreted sizeable amounts of osteocalcin and osteopontin between days 13 and 15 of culture. EDs were added at day 13 of culture at concentrations ranging from 10(-10) to 10(-6) M, being the culture medium deprived of FCS, and their effects were tested 48 h later. None of EDs was found to affect osteocalcin and osteopontin secretion from ROB cells, suggesting that their effects were tested at a relatively earlier stage of culture, when ROB cell differentiation into osteoblats is not fully accomplished, and/or the presence of estrogens contained in FCS is needed for EDs to exert their osteoblast-differentiation modulating action. BSP and BP3, but not resveratrol and silymarin, decreased proliferative activity of cultured ROB cells, a cytotoxic effect conceivably independent of their estrogen-receptor modulating activity. 相似文献
122.
Furfaro AL Macay JR Marengo B Nitti M Parodi A Fenoglio D Marinari UM Pronzato MA Domenicotti C Traverso N 《Free radical biology & medicine》2012,52(2):488-496
Cancer cell survival is known to be related to the ability to counteract oxidative stress, and glutathione (GSH) depletion has been proposed as a mechanism to sensitize cells to anticancer therapy. However, we observed that GI-ME-N cells, a neuroblastoma cell line without MYCN amplification, are able to survive even if GSH-depleted by l-buthionine-(S,R)-sulfoximine (BSO). Here, we show that in GI-ME-N cells, BSO activates Nrf2 and up-regulates heme oxygenase-1 (HO-1). Silencing of Nrf2 restrained HO-1 induction by BSO. Inhibition of HO-1 and silencing of Nrf2 or HO-1 sensitized GI-ME-N cells to BSO, leading to reactive oxygen/nitrogen species overproduction and decreasing viability. Moreover, targeting the Nrf2/HO-1 axis sensitized GI-ME-N cells to etoposide more than GSH depletion. Therefore, we have provided evidence that in GI-ME-N cells, the Nrf2/HO-1 axis plays a crucial role as a protective factor against cellular stress, and we suggest that the inhibition of Nfr2/HO-1 signaling should be considered as a central target in the clinical battle against neuroblastoma. 相似文献
123.
Gu G Barone I Gelsomino L Giordano C Bonofiglio D Statti G Menichini F Catalano S Andò S 《Journal of cellular physiology》2012,227(10):3363-3372
Breast cancer is the most frequent tumor and a major cause of death among women. Estrogens play a crucial role in breast tumor growth, which is the rationale for the use of hormonal antiestrogen therapies. Unfortunately, not all therapeutic modalities are efficacious and it is imperative to develop new effective antitumoral drugs. Oldenlandia diffusa (OD) is a well-known medicinal plant used to prevent and treat many disorders, especially cancers. The aim of this study was to investigate the effects of OD extracts on breast cancer cell proliferation. We observed that OD extracts strongly inhibited anchorage-dependent and -independent cell growth and induced apoptosis in estrogen receptor alpha (ERα)-positive breast cancer cells, whereas proliferation and apoptotic responses of MCF-10A normal breast epithelial cells were unaffected. Mechanistically, OD extracts enhance the tumor suppressor p53 expression as a result of an increased binding of ERα/Sp1 complex to the p53 promoter region. Finally, we isolated ursolic and oleanolic acids as the bioactive compounds able to upregulate p53 expression and inhibit breast cancer cell growth. These acids were greatly effective in reducing tamoxifen-resistant growth of a derivative MCF-7 breast cancer cell line resistant to the antiestrogen treatment. Our results evidence how OD, and its bioactive compounds, exert antiproliferative and apoptotic effects selectively in ERα-positive breast cancer cells, highlighting the potential use of these herbal extracts as breast cancer preventive and/or therapeutic agents. 相似文献
124.
Margalith I Suter C Ballmer B Schwarz P Tiberi C Sonati T Falsig J Nyström S Hammarström P Aslund A Nilsson KP Yam A Whitters E Hornemann S Aguzzi A 《The Journal of biological chemistry》2012,287(23):18872-18887
Luminescent conjugated polymers (LCPs) interact with ordered protein aggregates and sensitively detect amyloids of many different proteins, suggesting that they may possess antiprion properties. Here, we show that a variety of anionic, cationic, and zwitterionic LCPs reduced the infectivity of prion-containing brain homogenates and of prion-infected cerebellar organotypic cultured slices and decreased the amount of scrapie isoform of PrP(C) (PrP(Sc)) oligomers that could be captured in an avidity assay. Paradoxically, treatment enhanced the resistance of PrP(Sc) to proteolysis, triggered the compaction, and enhanced the resistance to proteolysis of recombinant mouse PrP(23-231) fibers. These results suggest that LCPs act as antiprion agents by transitioning PrP aggregates into structures with reduced frangibility. Moreover, ELISA on cerebellar organotypic cultured slices and in vitro conversion assays with mouse PrP(23-231) indicated that poly(thiophene-3-acetic acid) may additionally interfere with the generation of PrP(Sc) by stabilizing the conformation of PrP(C) or of a transition intermediate. Therefore, LCPs represent a novel class of antiprion agents whose mode of action appears to rely on hyperstabilization, rather than destabilization, of PrP(Sc) deposits. 相似文献
125.
126.
Piacente F Marin M Molinaro A De Castro C Seltzer V Salis A Damonte G Bernardi C Claverie JM Abergel C Tonetti M 《The Journal of biological chemistry》2012,287(5):3009-3018
Mimivirus is one the largest DNA virus identified so far, infecting several Acanthamoeba species. Analysis of its genome revealed the presence of a nine-gene cluster containing genes potentially involved in glycan formation. All of these genes are co-expressed at late stages of infection, suggesting their role in the formation of the long fibers covering the viral surface. Among them, we identified the L136 gene as a pyridoxal phosphate-dependent sugar aminotransferase. This enzyme was shown to catalyze the formation of UDP-4-amino-4,6-dideoxy-D-glucose (UDP-viosamine) from UDP-4-keto-6-deoxy-D-glucose, a key compound involved also in the biosynthesis of L-rhamnose. This finding further supports the hypothesis that Mimivirus encodes a glycosylation system that is completely independent of the amoebal host. Viosamine, together with rhamnose, (N-acetyl)glucosamine, and glucose, was found as a major component of the viral glycans. Most of the sugars were associated with the fibers, confirming a capsular-like nature of the viral surface. Phylogenetic analysis clearly indicated that L136 was not a recent acquisition from bacteria through horizontal gene transfer, but it was acquired very early during evolution. Implications for the origin of the glycosylation machinery in giant DNA virus are also discussed. 相似文献
127.
JH Lee JM Lee EM Ramos T Gillis JS Mysore S Kishikawa T Hadzi AE Hendricks MR Hayden PJ Morrison M Nance CA Ross RL Margolis F Squitieri C Gellera E Gomez-Tortosa C Ayuso O Suchowersky RJ Trent E McCusker A Novelletto M Frontali R Jones T Ashizawa S Frank MH Saint-Hilaire SM Hersch HD Rosas D Lucente MB Harrison A Zanko RK Abramson K Marder J Sequeiros G Bernhard Landwehrmeyer;On behalf of the Registry Study of the European Huntington’s Disease Network 《Biochemical and biophysical research communications》2012,426(3):404-408
128.
129.
Bianchi A Ugazzi M Ferrante L Lecis D Scavullo C Mastrangelo E Seneci P 《Bioorganic & medicinal chemistry letters》2012,22(6):2204-2208
A set of phenyl-substituted Smac mimetics/IAP inhibitor analogues of lead compound 2a was synthesized, aiming to retain its strong cell-free potency while increasing its bioavailability. Seventeen compounds 2b-r were prepared and characterized in vitro, using cell-free and cellular assays. Among them, the p-CF(3) substituted analogue 2m showed the best permeability through cell membranes, and was selected for further in vitro and in vivo studies due to its strong, sub-micromolar cellular potency. 相似文献
130.
Ginkgo biloba responds to herbivory by activating early signaling and direct defenses 总被引:1,自引:0,他引:1
Mohanta TK Occhipinti A Atsbaha Zebelo S Foti M Fliegmann J Bossi S Maffei ME Bertea CM 《PloS one》2012,7(3):e32822