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941.
U. Gómez-Pinedo L. Galán M. Yañez J. Matias-Guiu C. Valencia A. Guerrero-Sola F. Lopez-Sosa J.R. Brin M.S. Benito-Martin G. Leon-Espinosa A. Vela-Souto C. Lendinez T. Guillamon-Vivancos J.A. Matias-Guiu J.A. Arranz-Tagarro J.A. Barcia A.G. Garcia 《Neurología (Barcelona, Spain)》2018,33(4):211-223
Introduction
Cerebrospinal fluid (CSF) from amyotrophic lateral sclerosis (ALS) patients induces cytotoxic effects in in vitro cultured motor neurons.Material and methods
We selected CSF with previously reported cytotoxic effects from 32 ALS patients. Twenty-eight adult male rats were intracerebroventricularly implanted with osmotic mini-pumps and divided into 3 groups: 9 rats injected with CSF from non-ALS patients, 15 rats injected with cytotoxic ALS-CSF, and 4 rats injected with a physiological saline solution. CSF was intracerebroventricularly and continuously infused for periods of 20 or 43 days after implantation. We conducted clinical assessments and electromyographic examinations, and histological analyses were conducted in rats euthanised 20, 45, and 82 days after surgery.Results
Immunohistochemical studies revealed tissue damage with similar characteristics to those found in the sporadic forms of ALS, such as overexpression of cystatin C, transferrin, and TDP-43 protein in the cytoplasm. The earliest changes observed seemed to play a protective role due to the overexpression of peripherin, AKTpan, AKTphospho, and metallothioneins; this expression had diminished by the time we analysed rats euthanised on day 82, when an increase in apoptosis was observed. The first cellular changes identified were activated microglia followed by astrogliosis and overexpression of GFAP and S100B proteins.Conclusion
Our data suggest that ALS could spread through CSF and that intracerebroventricular administration of cytotoxic ALS-CSF provokes changes similar to those found in sporadic forms of the disease. 相似文献942.
Kaj Gijsbertse Max Bakker André Sprengers Juerd Wijntjes Saskia Lassche Nico Verdonschot Chris L. de Korte Nens van Alfen 《Clinical neurophysiology》2018,129(12):2567-2576
Objective
To develop an automated algorithm for detecting fasciculations and other movements in muscle ultrasound videos. Fasciculation detection in muscle ultrasound is routinely performed online by observing the live videos. However, human observation limits the objective information gained. Automated detection of movement is expected to improved sensitivity and specificity and increase reliability.Methods
We used 42 ultrasound videos from 11 neuromuscular patients for an iterative learning process between human observers and automated computer analysis, to identify muscle ultrasound movements. Two different datasets were selected from this, one to develop the algorithm and one to validate it. The outcome was compared to manual movement identification by clinicians. The algorithm also quantifies specific parameters of different movement types, to enable automated differentiation of events.Results
The algorithm reliably detected fasciculations. With algorithm guidance, observers found more fasciculations compared to visual analysis alone, and prescreening the videos with the algorithm saved clinicians significant time compared to reviewing full video sequences. All videos also contained other movements, especially contraction pseudotremor, which confused human interpretation in some.Conclusions
Automated movement detection is a feasible and attractive method to screen for fasciculations in muscle ultrasound videos.Significance
Our findings affirm the potential clinical usefulness of automated movement analysis in muscle ultrasound. 相似文献943.
944.
Thomas Meyer Erma Salkic Torsten Grehl Ute Weyen Dagmar Kettemann Patrick Weydt René Günther Paul Lingor Jan Christoph Koch Susanne Petri Andreas Hermann Johannes Prudlo Julian Großkreutz Petra Baum Matthias Boentert Moritz Metelmann Jenny Norden Isabell Cordts Jochen H. Weishaupt Johannes Dorst Albert Ludolph Yasemin Koc Bertram Walter Christoph Münch Susanne Spittel Marie Dreger André Maier Péter Körtvélyessy 《European journal of neurology》2023,30(6):1600-1610
Background and purpose
The objective was to assess the performance of serum neurofilament light chain (sNfL) in amyotrophic lateral sclerosis (ALS) in a wide range of disease courses, in terms of progression, duration and tracheostomy invasive ventilation (TIV).Methods
A prospective cross-sectional study at 12 ALS centers in Germany was performed. sNfL concentrations were age adjusted using sNfL Z scores expressing the number of standard deviations from the mean of a control reference database and correlated to ALS duration and ALS progression rate (ALS-PR), defined by the decline of the ALS Functional Rating Scale.Results
In the total ALS cohort (n = 1378) the sNfL Z score was elevated (3.04; 2.46–3.43; 99.88th percentile). There was a strong correlation of sNfL Z score with ALS-PR (p < 0.001). In patients with long (5–10 years, n = 167) or very long ALS duration (>10 years, n = 94) the sNfL Z score was significantly lower compared to the typical ALS duration of <5 years (n = 1059) (p < 0.001). Furthermore, in patients with TIV, decreasing sNfL Z scores were found in correlation with TIV duration and ALS-PR (p = 0.002; p < 0.001).Conclusions
The finding of moderate sNfL elevation in patients with long ALS duration underlined the favorable prognosis of low sNfL. The strong correlation of sNfL Z score with ALS-PR strengthened its value as progression marker in clinical management and research. The lowering of sNfL in correlation with long TIV duration could reflect a reduction either in disease activity or in the neuroaxonal substrate of biomarker formation during the protracted course of ALS. 相似文献945.
946.
《Resuscitation》2015
BackgroundStudies have shown that blended approaches combining e-learning with face-to-face training reduces costs whilst maintaining similar learning outcomes. The preferences in learning approach for healthcare providers to this new style of learning have not been comprehensively studied. The aim of this study is to evaluate the acceptability of blended learning to advanced resuscitation training.MethodsParticipants taking part in the traditional and blended electronic advanced life support (e-ALS) courses were invited to complete a written evaluation of the course. Participants’ views were captured on a 6-point Likert scale and in free text written comments covering the content, delivery and organisation of the course. Proportional-odds cumulative logit models were used to compare quantitative responses. Thematic analysis was used to synthesise qualitative feedback.Results2848 participants from 31 course centres took part in the study (2008–2010). Candidates consistently scored content delivered face-to-face over the same content delivered over the e-learning platform. Candidates valued practical hands on training which included simulation highly. Within the e-ALS group, a common theme was a feeling of “time pressure” and they “preferred the face-to-face teaching”. However, others felt that e-ALS “suited their learning style”, was “good for those recertifying”, and allowed candidates to “use the learning materials at their own pace”.ConclusionsThe e-ALS course was well received by most, but not all participants. The majority felt the e-learning module was beneficial. There was universal agreement that the face-to-face training was invaluable. Individual learning styles of the candidates affected their reaction to the course materials. 相似文献
947.
948.
Cassandra N. Dennys Florence Roussel Rochelle Rodrigo Xiaojin Zhang Andrea Sierra Delgado Annalisa Hartlaub Asya Saelim-Ector Will Ray Sarah Heintzman Ashley Fox Stephen J. Kolb Joseph Beckman Maria Clara Franco Kathrin Meyer 《Glia》2023,71(2):350-365
Patient diversity and unknown disease cause are major challenges for drug development and clinical trial design for amyotrophic lateral sclerosis (ALS). Transgenic animal models do not adequately reflect the heterogeneity of ALS. Direct reprogramming of patient fibroblasts to neuronal progenitor cells and subsequent differentiation into patient astrocytes allows rapid generation of disease relevant cell types. Thus, this methodology can facilitate compound testing in a diverse genetic background resulting in a more representative population for therapeutic evaluation. Here, we used established co-culture assays with motor neurons and reprogrammed patient skin-derived astrocytes (iAs) to evaluate the effects of (SP-4-2)-[[2,2’-(1,2-dimethyl-1,2-ethanediylidene)bis[N-methylhydrazinecarbothioamidato-κN2,κS]](2-)]-copper (CuATSM), currently in clinical trial for ALS in Australia. Pretreatment of iAs with CuATSM had a differential effect on neuronal survival following co-culture with healthy motor neurons. Using this assay, we identified responding and non-responding cell lines for both sporadic and familial ALS (mutant SOD1 and C9ORF72). Importantly, elevated mitochondrial respiration was the common denominator in all CuATSM-responders, a metabolic phenotype not observed in non-responders. Pre-treatment of iAs with CuATSM restored mitochondrial activity to levels comparable to healthy controls. Hence, this metabolic parameter might allow selection of patient subpopulations best suited for CuATSM treatment. Moreover, CuATSM might have additional therapeutic value for mitochondrial disorders. Enhanced understanding of patient-specific cellular and molecular profiles could help improve clinical trial design in the future. 相似文献
949.
Federica Solca Edoardo Nicolò Aiello Silvia Torre Laura Carelli Roberta Ferrucci Federico Verde Nicola Ticozzi Vincenzo Silani Alessia Monti Barbara Poletti 《European journal of neurology》2023,30(3):606-611
Background and purpose
This study aimed at estimating the prevalence of language impairment (LI) in a large, clinic-based cohort of non-demented amyotrophic lateral sclerosis (ALS) patients and assessing its underpinnings at motor and non-motor levels.Methods
Non-demented ALS patients (N = 348) underwent the Edinburgh Cognitive and Behavioural ALS Screen (ECAS), as well as an assessment of behavioural/psychiatric and motor-functional features. The prevalence of LI was estimated based on the proportion of patients showing a performance below the age- and education-adjusted cut-off on the ECAS-Language. Multiple regression models were run to assess the determinants of language functioning and impairment.Results
The prevalence of LI was 22.7%. 46.6% of the variance of ECAS-Language scores remained unexplained, with only the ECAS-Executive positively predicting them (p < 0.001; η2 = 0.07). Similarly, only a lower score on the ECAS-Executive predicted a higher probability of a below cut-off ECAS-Language performance (p < 0.001). Spelling and Naming tasks were the major drivers of ECAS-Language performance.Conclusions
This study suggests that, in non-demented ALS patients, LI occurs in ≈23% of cases, is significantly driven by executive dysfunction but, at the same time, partially independent of it and is not associated with other motor or non-motor features. 相似文献950.