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81.
82.
Amal M. Mohamed Tarek F. Elwakil Ibrahim M. Taher Mohamed M. Elbarbary Hesham F. Kayed Hassan A. Hussein Ola M. Eid 《Cell and tissue research》2009,338(1):107-115
Cyclin D1 gene amplification has been reported to promote abnormal endothelial cell proliferation and angiogenesis; these
findings constantly present in proliferating haemangiomas. The present study was conducted to evaluate cyclin D1 gene amplification
by fluorescence in situ hybridization analysis in tissue biopsies of 22 proliferating haemangiomas from 20 infants. Two significant
correlations of cyclin D1 gene amplification with the early onset and the duplication of proliferating haemangiomas have been
observed. Moreover, a significant correlation (P≤0.05) has been found between the treatment parameters of proliferating haemangiomas with the amplified versus the normal
cyclin D1 gene. Proliferating haemangiomas with the amplified cyclin D1 gene required more frequent flashlamp pulsed dye laser
treatment sessions at the maximum dosimetry and more frequent intralesional steroid injections at the maximum dose/injection
but treatment outcomes were limited. The more frequent post-treatment complications among proliferating haemangiomas with
cyclin D1 gene amplification might be attributable not only to the associated more aggressive natural course, but also to
the higher treatment parameters needed for effective treatment. Within the limitations of the present study, cyclin D1 gene
amplification was seen for the first time in proliferating haemangiomas. We have found that the amplification of the cyclin
D1 gene can predict the more aggressive natural course of proliferating haemangiomas and the limited outcome and higher incidence
of complications after non–excision treatment modalities. The present findings reflect the possible usefulness of antisense
cyclin D1 to improve the therapeutic outcome of proliferating haemangiomas. 相似文献
83.
David V. Smil Sukhdev Manku Yves A. Chantigny Silvana Leit Amal Wahhab Theresa P. Yan Marielle Fournel Christiane Maroun Zuomei Li Anne-Marie Lemieux Alina Nicolescu Jubrail Rahil Sylvain Lefebvre Anthony Panetta Jeffrey M. Besterman Robert Déziel 《Bioorganic & medicinal chemistry letters》2009,19(3):688-692
In an effort to identify HDAC isoform selective inhibitors, we designed and synthesized novel, chiral 3,4-dihydroquinoxalin-2(1H)-one and piperazine-2,5-dione aryl hydroxamates showing selectivity (up to 40-fold) for human HDAC6 over other class I/IIa HDACs. The observed selectivity and potency (IC50 values 10–200 nM against HDAC6) is markedly dependent on the absolute configuration of the chiral moiety, and suggests new possibilities for use of chiral compounds in selective HDAC isoform inhibition. 相似文献
84.
Ping La Amal P. Fernando Zhi Wang Ameen Salahudeen Guang Yang Qing Lin Clyde J. Wright Phyllis A. Dennery 《The Journal of biological chemistry》2009,284(52):36302-36311
Zinc protoporphyrin IX (ZnPP), an endogenous heme analogue that inhibits heme oxygenase (HO) activity, represses tumor growth. It can also translocate into the nucleus and up-regulate heme oxygenase 1 (HMOX1) gene expression. Here, we demonstrate that tumor cell proliferation was inhibited by ZnPP, whereas tin protoporphyrin (SnPP), another equally potent HO-1 inhibitor, had no effect. Microarray analysis on 128 tumorigenesis related genes showed that ZnPP suppressed genes involved in cell proliferation and angiogenesis. Among these genes, CYCLIN D1 (CCND1) was specifically inhibited as were its mRNA and protein levels. Additionally, ZnPP inhibited CCND1 promoter activity through an Sp1 and Egr1 overlapping binding site (S/E). We confirmed that ZnPP modulated the S/E site, at least partially by associating with Sp1 and Egr1 proteins rather than direct binding to DNA targets. Furthermore, administration of ZnPP significantly inhibited cyclin D1 expression and progression of a B-cell leukemia/lymphoma 1 tumor in mice by preferentially targeting tumor cells. These observations show HO independent effects of ZnPP on cyclin D1 expression and tumorigenesis. 相似文献
85.
86.
Poor drug solubility and dissolution rate remain to be one of the major problems facing pharmaceutical scientists, with approximately 40% of drugs in the industry categorised as practically insoluble or poorly water soluble. This in turn can lead to serious delivery challenges and poor bioavailability. The aim of this research was to investigate the effects of the surfactants, poloxamer 407 (P407) and caprol® PGE 860 (CAP), at various concentrations (0.1, 0.5, 1 and 3% w/v) on the enhancement of the dissolution properties of poorly water-soluble drug, naproxen, using in situ micronisation by solvent change method and freeze-drying. The extent at which freeze-drying influences the dissolution rate of naproxen microcrystals is investigated in this study by comparison with desiccant-drying. All formulations were evaluated and characterised using particle size analysis and morphology, in vitro dissolution studies, differential scanning calorimetry (DSC), and Fourier transform infra-red (FT-IR) spectroscopy. An increase in poloxamer 407 concentration in freeze-dried formulations led to enhancement of drug dissolution compared to desiccator-dried formulations, naproxen/caprol® PGE 860 formulations and untreated drug. DSC and FT-IR results show no significant chemical interactions between drug and poloxamer 407, with only very small changes to drug crystallinity. On the other hand, caprol® PGE 860 showed some interactions with drug components, alterations to the crystal lattice of naproxen, and poor dissolution profiles using both drying methods, making it a poor choice of excipient. 相似文献
87.
Fungal endophytes: unique plant inhabitants with great promises 总被引:2,自引:0,他引:2
Fungal endophytes residing in the internal tissues of living plants occur in almost every plant on earth from the arctic to
the tropics. The endophyte–host relationship is described as a balanced symbiotic continuum ranging from mutualism through
commensalism to parasitism. This overview will highlight selected aspects of endophyte diversity, host specificity, endophyte–host
interaction and communication as well as regulation of secondary metabolite production with emphasis on advanced genomic methods
and their role in improving our current knowledge of endophytic associations. Furthermore, the chemical potential of endophytic
fungi for drug discovery will be discussed with focus on the detection of pharmaceutically valuable plant constituents as
products of fungal biosynthesis. In addition, selected examples of bioactive metabolites reported in recent years (2008–2010)
from fungal endophytes residing in terrestrial plants are presented grouped according to their reported biological activities. 相似文献
88.
Najjar A Robert S Guérin C Violet-Asther M Carrière F 《Applied microbiology and biotechnology》2011,89(6):1947-1962
Lipase secretion, extracellular lipolysis, and fatty acid uptake were quantified in the yeast Yarrowia lipolytica grown in the presence of olive oil and/or glucose. Specific lipase assays, Western blot analysis, and ELISA indicated that
most of the lipase activity measured in Y. lipolytica cultures resulted from the YLLIP2 lipase. Lipase production was triggered by olive oil and, during the first hours of culture,
most of the lipase activity and YLLIP2 immunodetection remained associated with the yeast cells. YLLIP2 was then released
in the culture medium before it was totally degraded by proteases. Olive oil triglycerides were largely degraded when the
lipase was still attached to the cell wall. The fate of lipolysis products in the culture medium and inside the yeast cell,
as well as lipid storage, was investigated simultaneously by quantitative TLC–FID and GC analysis. The intracellular levels
of free fatty acids (FFA) and triglycerides increased transiently and were dependent on the carbon sources. A maximum fat
storage of 37.8% w/w of yeast dry mass was observed with olive oil alone. A transient accumulation of saturated FFA was observed whereas intracellular
triglycerides became enriched in unsaturated fatty acids. So far, yeasts have been mainly used for studying the intracellular
synthesis, storage, and mobilization of neutral lipids. The present study shows that yeasts are also interesting models for
studying extracellular lipolysis and fat uptake by the cell. The quantitative data obtained here allow for the first time
to establish interesting analogies with gastrointestinal and vascular lipolysis in humans. 相似文献
89.
90.
Dutta AK Khimji AK Kresge C Bugde A Dougherty M Esser V Ueno Y Glaser SS Alpini G Rockey DC Feranchak AP 《The Journal of biological chemistry》2011,286(1):766-776
Cl(-) channels in the apical membrane of biliary epithelial cells (BECs) provide the driving force for ductular bile formation. Although a cystic fibrosis transmembrane conductance regulator has been identified in BECs and contributes to secretion via secretin binding basolateral receptors and increasing [cAMP](i), an alternate Cl(-) secretory pathway has been identified that is activated via nucleotides (ATP, UTP) binding apical P2 receptors and increasing [Ca(2+)](i). The molecular identity of this Ca(2+)-activated Cl(-) channel is unknown. The present studies in human, mouse, and rat BECs provide evidence that TMEM16A is the operative channel and contributes to Ca(2+)-activated Cl(-) secretion in response to extracellular nucleotides. Furthermore, Cl(-) currents measured from BECs isolated from distinct areas of intrahepatic bile ducts revealed important functional differences. Large BECs, but not small BECs, exhibit cAMP-stimulated Cl(-) currents. However, both large and small BECs express TMEM16A and exhibit Ca(2+)-activated Cl(-) efflux in response to extracellular nucleotides. Incubation of polarized BEC monolayers with IL-4 increased TMEM16A protein expression, membrane localization, and transepithelial secretion (I(sc)). These studies represent the first molecular identification of an alternate, noncystic fibrosis transmembrane conductance regulator, Cl(-) channel in BECs and suggest that TMEM16A may be a potential target to modulate bile formation in the treatment of cholestatic liver disorders. 相似文献