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881.
Effects of antiepileptic drugs on induced epileptiform activity in a rat model of dysplasia 总被引:2,自引:0,他引:2
Seizure activity associated with cortical dysplasia (CD) is often resistant to standard pharmacologic treatments. Although several animal models exhibit CD, virtually nothing is known about antiepileptic drug (AED) responses in these animals. Here we have used rats exposed to methylazoxymethanol acetate (MAM) in utero, an animal model featuring nodular heterotopia, to investigate the effects of AEDs in the dysplastic brain. 4-aminopyridine (100 μM), a K+ channel blocker, was used to induce interictal epileptiform bursting in acute hippocampal slices from MAM-exposed and age-matched vehicle-injected control animals. Extracellular field recordings were used to monitor seizure activity in vitro. Five commonly used AEDs were tested: phenobarbital, 25–400 μM; carbamazepine, 25–200 μM; valproate (VPA), 0.19–4 mM; ethosuximide (ESM), 0.5–8 mM; and lamotrigine (LTG), 49–390 μM. 4-AP-induced bursting occurred with shorter latencies in slices from MAM-exposed rats in comparison with slices from controls, confirming the intrinsic hyperexcitability of dysplastic tissue. Each AED tested demonstrated significant burst suppression in control slices, but interictal epileptiform bursting in MAM-exposed slices was resistant to these treatments. Even at the highest concentrations, VPA, ESM and LTG had no effect on burst amplitude in slices from MAM-exposed rats. Pharmaco-resistance was further tested by measuring seizure latencies in awake, freely-moving rats after kainate administration (15 mg/kg, i.p.) with and without pre-treatment with VPA (400 mg/kg i.p.). Pre-treatment with VPA prolonged seizure latency in control rats, but had no effect in MAM-exposed animals. These results suggest MAM-exposed rats exhibit a dramatically reduced sensitivity to commonly prescribed AEDs. 相似文献
882.
Robert Fisher Vicenta Salanova Thomas Witt Robert Worth Thomas Henry Robert Gross Kalarickal Oommen Ivan Osorio Jules Nazzaro Douglas Labar Michael Kaplitt Michael Sperling Evan Sandok John Neal Adrian Handforth John Stern Antonio DeSalles Steve Chung Andrew Shetter Donna Bergen Roy Bakay Jaimie Henderson Jacqueline French Gordon Baltuch William Rosenfeld Andrew Youkilis William Marks Paul Garcia Nicolas Barbaro Nathan Fountain Carl Bazil Robert Goodman Guy McKhann K. Babu Krishnamurthy Steven Papavassiliou Charles Epstein John Pollard Lisa Tonder Joan Grebin Robert Coffey Nina Graves 《Epilepsia》2010,51(5):899-908
Purpose: We report a multicenter, double‐blind, randomized trial of bilateral stimulation of the anterior nuclei of the thalamus for localization‐related epilepsy. Methods: Participants were adults with medically refractory partial seizures, including secondarily generalized seizures. Half received stimulation and half no stimulation during a 3‐month blinded phase; then all received unblinded stimulation. Results: One hundred ten participants were randomized. Baseline monthly median seizure frequency was 19.5. In the last month of the blinded phase the stimulated group had a 29% greater reduction in seizures compared with the control group, as estimated by a generalized estimating equations (GEE) model (p = 0.002). Unadjusted median declines at the end of the blinded phase were 14.5% in the control group and 40.4% in the stimulated group. Complex partial and “most severe” seizures were significantly reduced by stimulation. By 2 years, there was a 56% median percent reduction in seizure frequency; 54% of patients had a seizure reduction of at least 50%, and 14 patients were seizure‐free for at least 6 months. Five deaths occurred and none were from implantation or stimulation. No participant had symptomatic hemorrhage or brain infection. Two participants had acute, transient stimulation‐associated seizures. Cognition and mood showed no group differences, but participants in the stimulated group were more likely to report depression or memory problems as adverse events. Discussion: Bilateral stimulation of the anterior nuclei of the thalamus reduces seizures. Benefit persisted for 2 years of study. Complication rates were modest. Deep brain stimulation of the anterior thalamus is useful for some people with medically refractory partial and secondarily generalized seizures. 相似文献
883.
Suhy J Laxer KD Capizzano AA Vermathen P Matson GB Barbaro NM Weiner MW 《Neurology》2002,58(5):821-823
1H MRS imaging (MRSI) was performed on 15 patients with MRI-negative temporal lobe epilepsy (TLE) who underwent seizure surgery. The non-seizure-free patients (NSF) ipsilateral hippocampal N-acetylaspartate (NAA)/(Cr+Cho) z scores were lower than the contralateral scores (p = 0.04), and the NSF ipsilateral z scores were lower than the seizure-free patients' (SF) ipsilateral z scores (p = 0.0049). Similarly, NSF contralateral scores were lower than contralateral SF (p = 0.02). These findings suggest NAA predicts the surgical outcome in patients with TLE without evidence of mesial temporal sclerosis on MRI. 相似文献
884.
885.
Giovanni Di Nardo Cesare Cremon Annamaria Staiano Vincenzo Stanghellini Osvaldo Borrelli Caterina Strisciuglio Claudio Romano Saverio Mallardo Elena Scarpato Giovanni Marasco Silvia Salvatore Letizia Zenzeri Enrico Felici Licia Pensabene Simona Sestito Ruggiero Francavilla Paolo Quitadamo Mariella Baldassarre Valentina Giorgio Renato Tambucci Chiara Ziparo Pasquale Parisi Maria Raffaella Barbaro Giovanni Barbara Neurogastroenterology Study Group of the Italian Society of Pediatric Gastroenterology Hepatology Nutrition 《Neurogastroenterology and motility》2023,35(3):e14365