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Harry G. Brittain 《Journal of pharmaceutical sciences》2011,100(4):1260-1279
Research papers and issued patents involving polymorphism (i.e., crystal systems for which a substance can exist in structures characterized by different unit cells, but in which each of the forms has exactly the same elemental composition) and solvatomorphism (i.e., systems in which the crystal structures of the substance are defined by different unit cells, but wherein these unit cells differ in their elemental composition through the inclusion of one or more molecules of solvent) have been summarized in an annual review. The works cited in this review were published during 2009, and were sourced from the major physical, crystallographic, and pharmaceutical journals. The review is divided into sections that cover articles of general interest, computational and theoretical studies, preparative and isolation methods, structural characterization, properties of polymorphic and solvatomorphic systems, studies of phase transformations, effects associated with secondary processing, and US patents issued during 2009. 相似文献
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Perez Alexander Brittain Kirsty Phillips Nicole Stein Dan J. Zar Heather J. Myer Landon Hoare Jacqueline 《AIDS and behavior》2022,26(2):434-442
AIDS and Behavior - The effect of chronic HIV-infection on psychological adjustment, including the impact of HIV-related stigma in perinatally HIV-infected (PHIV+) youth across Africa is largely... 相似文献
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Zhen EY Brittain IJ Laska DA Mitchell PG Sumer EU Karsdal MA Duffin KL 《Arthritis and rheumatism》2008,58(8):2420-2431
OBJECTIVE: To identify, characterize, and compare proteolysis peptide products generated by metalloprotease digests of human articular cartilage. METHODS: Human articular cartilage was digested by the addition of exogenous metalloproteases, including matrix metalloproteinases 2, 3, 8, 9, 12, and 13 and aggrecanases ADAMTS-4 and ADAMTS-5. Proteolyzed peptide products were identified by proteomics methods using mass spectrometry. RESULTS: Complete sequences of the peptides proteolyzed from human articular cartilage, including N- and C-termini and hydroxylated posttranslational modifications, were determined. A wide variety of peptides, originating from types I, II, and III collagen, biglycan, prolargin, fibromodulin, fibronectin, decorin, cartilage oligomeric matrix protein, cartilage intermediate-layer protein, megakaryocyte-stimulating factor, mimecan, aggrecan, and lumican, was analyzed following metalloprotease digestion. Release of peptides varied as a function of time, enzyme specificity, and abundance. Specific type II collagen peptide biomarkers, including those containing the three-quarter-length fragment cleavage site and those containing the domains for helical peptide of type II collagen and C-telopeptide of type II collagen, were observed after release by selected proteases. CONCLUSION: The use of intact cartilage instead of purified protein substrates in the assay allowed for the identification of novel potential substrates and cleavage sites for individual enzymes under more physiologically relevant conditions. Characterization of these cartilage matrix peptides may help in the development of pharmacodynamic biomarkers of cartilage degradation, and also may contribute to an understanding of the bioactive peptides important in chondrocyte signaling. 相似文献
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Raed A. Joundi John-Stuart Brittain Alex L. Green Tipu Z. Aziz Peter Brown Ned Jenkinson 《Clinical neurophysiology》2013,124(3):565-573
ObjectiveThe function of synchronous oscillatory activity at beta band (15–30 Hz) frequencies within the basal ganglia is unclear. Here we sought support for the hypothesis that beta activity has a global function within the basal ganglia and is not directly involved in the coding of specific biomechanical parameters of movement.MethodsWe recorded local field potential activity from the subthalamic nuclei of 11 patients with Parkinson’s disease during a synchronized tapping task at three different externally cued rates.ResultsBeta activity was suppressed during tapping, reaching a minimum that differed little across the different tapping rates despite an increase in velocity of finger movements. Thus beta power suppression was independent of specific motor parameters. Moreover, although beta oscillations remained suppressed during all tapping rates, periods of resynchronization between taps were markedly attenuated during high rate tapping. As such, a beta rebound above baseline between taps at the lower rates was absent at the high rate.ConclusionOur results demonstrate that beta desynchronization in the region of the subthalamic nucleus is independent of motor parameters and that the beta resynchronization is differentially modulated by rate of finger tapping,SignificanceThese findings implicate consistent beta suppression in the facilitation of continuous movement sequences. 相似文献
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Payal C. Desai Julia E. Brittain Susan K. Jones Adam McDonald Douglas R. Wilson Rosalie Dominik Nigel S. Key Leslie V. Parise Kenneth I. Ataga 《Thrombosis research》2013
Introduction
The contribution of platelet activation to the pathogenesis of sickle cell disease (SCD) remains uncertain. We evaluated the safety and efficacy of eptifibatide, a synthetic peptide inhibitor of the αIIbβ3 receptor, in SCD patients during acute painful episodes.Materials and Methods
In this single site, double-blind, placebo-controlled trial, eligible patients with SCD admitted for acute painful episodes were randomized to receive eptifibatide or placebo at a ratio of 2:1.Results
Thirteen patients (SS - 10, Sβ0 - 2, SC - 1) were randomized to receive either eptifibatide (N = 9; 6 females; median age - 25 years) or placebo (N = 4; 3 females; median age - 31 years). In the intent-to-treat analysis, there were no major bleeding episodes in either the eptifibatide or placebo arms (point estimate of difference: 0.00, 95% CI; -0.604, 0.372). There was one minor bleeding episode in the eptifibatide arm (point estimate of difference for any bleeding: 0.11, 95% CI: -0.502, 0.494). There was no significant difference in the proportion of patients with thrombocytopenia between the treatment groups (point estimate of difference: 0.11, 95% CI: -0.587, 0.495). There were no differences in the median times to discharge, median times to crisis resolution or the median total opioid use.Conclusions
In this small study, eptifibatide appeared to be safe, but did not improve the times to crisis resolution or hospital discharge. Adequately powered studies are required to evaluate the safety and efficacy of eptifibatide in SCD. Clinicaltrials.gov Identifier: NCT00834899. 相似文献19.
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Population Pharmacokinetic/ Pharmacodynamic Modelling of Auditory‐Evoked Event‐Related Potentials with Lorazepam
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Aurélie Lombard Claire Brittain Graham Wishart Stephen Lowe Andrew McCarthy William Landschulz Georg Dorffner Peter Anderer Eunice Yuen 《Basic & clinical pharmacology & toxicology》2018,122(2):245-252
Event‐related potentials (ERPs) are commonly used in Neuroscience research, particularly the P3 waveform because it is associated with cognitive brain functions and is easily elicited by auditory or sensory inputs. ERPs are affected by drugs such as lorazepam, which increase the latency and decrease the amplitude of the P3 wave. In this study, auditory‐evoked ERPs were generated in 13 older healthy volunteers using an oddball tone paradigm, after administration of single 0.5 and 2 mg doses of lorazepam. Population pharmacokinetics (PK)/pharmacodynamics (PD) models were developed using nonlinear mixed‐effects methods in order to assess the effect of lorazepam on the latency and amplitude of the P3 waveforms. The PK/PD models showed that doses of 0.3 mg of lorazepam achieved approximately half of the maximum effect on the latency of the P3 waveform. For P3 amplitude, half the maximum effect was achieved with a dose of 1.2 mg of lorazepam. The PK/PD models also predicted an efficacious dose range of lorazepam, which was close to the recommended therapeutic range. The use of longitudinal P3 latency data allowed better predictions of the lorazepam efficacious dose range than P3 amplitude or aggregate exposure–response data, suggesting that latency could be a more sensitive parameter for drugs with similar mechanisms of action as lorazepam and that time course rather than single time‐point ERP data should be collected. Overall, the results suggest that P3 ERP waveforms could be used as potential non‐specific biomarkers for functional target engagement for drugs with brain activity, and PK/PD models can aid trial design and choice of doses for development of new drugs with ERP activity. 相似文献