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61.
Airoldi F Di Mario C Takagi T Stankovic G Albiero R Colombo A 《International journal of cardiovascular interventions》2001,4(2):91-98
Based on the currently available data, the strategy of routine stent placement in unselected lesions located in small coronary arteries provides good immediate results but is still associated with a high incidence of in-stent restenosis. Randomized trials comparing elective stenting with balloon angioplasty have not provided the demonstration that routine stenting is the best strategy for percutaneous intervention in coronary arteries with a reference diameter smaller than 2.75-3.0 mm. This paper describes the rationale for provisional stenting in this clinical setting and reviews the role of quantitative coronary angiography, intracoronary ultrasound and intracoronary Doppler measurements in the identification of lesions that would benefit from adjunctive stent placement after balloon angioplasty and in guiding stent implantation. 相似文献
62.
Miljen Martić Lucile Pernot Yvonne Westermaier Remo Perozzo Tatjana Gazivoda Kraljević Svjetlana Krištafor 《Nucleosides, nucleotides & nucleic acids》2013,32(4):293-315
Novel C-6 substituted pyrimidine derivatives are good substrates of herpes simplex virus type 1 thymidine kinase (HSV1-TK). Enzyme kinetic experiments showed that our lead compound, N-methyl DHBT (N-methyl-6-(1,3-dihydroxyisobutyl) thymine; N-Me DHBT), is phosphorylated at a similar rate compared to “gold standard” 9-[4-fluoro-3-(hydroxymethyl)butyl]guanine, FHBG, (K m = 10 ± 0.3 μM; k cat = 0.036 ± 0.015 sec?1). Additionally, it does not show cytotoxic properties on B16F1 cells up to a concentration of 10 mM. The x-ray analysis of the crystal structures of HSV1-TK with N-Me DHBT and of HSV1-TK with the fluorinated derivative N-Me FHBT confirmed the binding mode predicted by docking studies and their substrate characteristics. Moreover, the crystal structure of HSV1-TK with N-Me DHBT revealed an additional water-mediated H-bond interesting for the design of further analogues. 相似文献
63.
Alessandro Grecucci Nicola De Pisapia Derangala Kusalagnana Thero Maria Paola Paladino Paola Venuti Remo Job 《PloS one》2015,10(1)
One of the consequences of extensive mindfulness practice is a reduction of anxiety and depression, but also a capacity to regulate negative emotions. In this study, we explored four key questions concerning mindfulness training: (1) What are the processes by which mindfulness regulates our emotions? (2) Can mindfulness be applied to social emotions? (3) Does mindfulness training affect emotionally driven behavior towards others? (4) Does mindfulness alter physiological reactivity? To address these questions, we tested, in two experiments, the ability of mindfulness meditators to regulate interpersonal emotions (Experiment 1) and interactive behaviors (Experiment 2) as compared to naïve controls. To better understand the mechanisms by which mindfulness regulates emotions, we asked participants to apply two strategies: a cognitive strategy (mentalizing, a form of reappraisal focused on the intentions of others) and an experiential strategy derived from mindfulness principles (mindful detachment). Both groups were able to regulate interpersonal emotions by means of cognitive (mentalizing) and experiential (mindful detachment) strategies. In Experiment 1, a simple effect of meditation, independent from the implementation of the strategies, resulted in reduced emotional and physiological reactivity, as well as in increased pleasantness for meditators when compared to controls, providing evidence of baseline regulation. In Experiment 2, one visible effect of the strategy was that meditators outperformed controls in the experiential (mindful detachment) but not in the cognitive (mentalize) strategy, showing stronger modulation of their interactive behavior (less punishments) and providing evidence of a strategic behavioral regulation. Based on these results, we suggest that mindfulness can influence interpersonal emotional reactions through an experiential mechanism, both at a baseline level and a strategic level, thereby altering the subjective and physiological perception of emotions, but also biasing interactive social behavior. 相似文献
64.
Kuettel S Greenwald J Kostrewa D Ahmed S Scapozza L Perozzo R 《PLoS neglected tropical diseases》2011,5(5):e1164
Background
The essential purine salvage pathway of Trypanosoma brucei bears interesting catalytic enzymes for chemotherapeutic intervention of Human African Trypanosomiasis. Unlike mammalian cells, trypanosomes lack de novo purine synthesis and completely rely on salvage from their hosts. One of the key enzymes is adenosine kinase which catalyzes the phosphorylation of ingested adenosine to form adenosine monophosphate (AMP) utilizing adenosine triphosphate (ATP) as the preferred phosphoryl donor.Methods and Findings
Here, we present the first structures of Trypanosoma brucei rhodesiense adenosine kinase (TbrAK): the structure of TbrAK in complex with the bisubstrate inhibitor P1,P5-di(adenosine-5′)-pentaphosphate (AP5A) at 1.55 Å, and TbrAK complexed with the recently discovered activator 4-[5-(4-phenoxyphenyl)-2H-pyrazol-3-yl]morpholine (compound 1) at 2.8 Å resolution.Conclusions
The structural details and their comparison give new insights into substrate and activator binding to TbrAK at the molecular level. Further structure-activity relationship analyses of a series of derivatives of compound 1 support the observed binding mode of the activator and provide a possible mechanism of action with respect to their activating effect towards TbrAK. 相似文献65.
The VP1 unique region (VP1u) of human parvovirus B19 (B19V) is the immunodominant part of the viral capsid. Originally inaccessible, the VP1u becomes exposed upon primary attachment to the globoside receptor. To study the function of the exposed VP1u in B19V uptake, we expressed this region as a recombinant protein. Here, we report that purified recombinant VP1u binds and is internalized in UT7/Epo cells. By means of truncations and specific antibodies, we identified the most N-terminal amino acid residues of VP1u as the essential region for binding and internalization. Furthermore, the recombinant VP1u was able to block B19V uptake, suggesting that the protein and the virus undertake the same internalization pathway. Assays with different erythroid and nonerythroid cell lines showed that the N-terminal VP1u binding was restricted to a few cell lines of the erythroid lineage, which were also the only cells that allowed B19V internalization and infection. These results together indicate that the N-terminal region of VP1u is responsible for the internalization of the virus and that the interacting receptor is restricted to B19V-susceptible cells. The highly selective uptake mechanism represents a novel determinant of the tropism and pathogenesis of B19V. 相似文献
66.
Campiche Remo Jackson Eileen Laurent Guillaume Roche Magalie Gougeon Sarah Séroul Pierre Ströbel Simon Massironi Marco Gempeler Mathias 《International journal of peptide research and therapeutics》2020,26(1):181-189
International Journal of Peptide Research and Therapeutics - Aging of skin manifests in loss of volume and firming due to degradation of extracellular matrix components such as collagen and... 相似文献
67.
Raluca Gordân Ning Shen Iris Dror Tianyin Zhou John Horton Remo Rohs Martha L. Bulyk 《Cell reports》2013,3(4):1093-1104
Highlights? Cbf1 and Tye7 are paralogous TFs with virtually identical DNA binding-site motifs ? The two paralogous TFs bind different genomic target sites in vivo ? The genomic context of putative DNA binding sites affects TF binding specificity ? Structural analyses suggest that genomic context influences TF binding through DNA shape 相似文献
68.
Cifani C Micioni Di Bonaventura MV Cannella N Fedeli A Guerrini R Calo G Ciccocioppo R Ubaldi M 《Peptides》2011,32(1):44-50
Neuropeptide S (NPS) is the endogenous ligand for the previously orphan G-protein-coupled-receptor, now termed NPS receptor (NPSR). NPS has both anxiolytic and pro-arousal properties and decreases food intake. In this work we use a rat model of palatable food intake to test in vivo different analogs of human NPS developed in our laboratories and characterized in previous in vitro experiments as partial agonists ([Ala3]NPS and [Aib5]NPS), or antagonists ([d-Cys(tBu)5]NPS and [tBu-d-Gly5]NPS). Our results confirmed that intracerebroventricular (ICV) injection of NPS (1 nmol) decreases standard chow intake in food restricted rats as well as in freely feeding animals fed with standard or palatable food diets. [Aib5]NPS (30 and 60 nmol), like NPS, reduced palatable food intake, thus confirming in vivo its ability to activate NPSR. [Ala3]NPS (60 nmol) did not affect palatable food intake per se but blocked the anorectic effect of NPS, thus suggesting its ability to function as an antagonist in this model. Finally, [d-Cys(tBu)5]NPS (20-60 nmol) and [tBu-d-Gly5]NPS (10-30 nmol), described in previous in vitro studies as pure NPSR antagonists, did not affect palatable food intake when given alone, but fully blocked the anorectic effect of NPS. These results provide an important characterization of the pharmacological properties of these NPS analogs in vivo. Of particular relevance are the data showing that [d-Cys(tBu)5]NPS and [tBu-d-Gly5]NPS behave as pure antagonists at NPSR regulating food intake, indicating that these molecules are suitable tools for further investigation of the physiopharmacology of the NPS/NPSR system. 相似文献
69.
70.
Caterina Gasperini Kiril Tuntevski Silvia Beatini Roberta Pelizzoli Amanda Lo Van Damiano Mangoni Rosa M Cossu Giovanni Pascarella Paolo Bianchini Pascal Bielefeld Margherita Scarpato Meritxell PonsEspinal Remo Sanges Alberto Diaspro Carlos P Fitzsimons Piero Carninci Stefano Gustincich Davide De Pietri Tonelli 《EMBO reports》2023,24(2)