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41.
Débora J. Pérez Germán Lukaszewicz Mirta L. Menone María V. Amé Elsa L. Camadro 《Environmental toxicology》2014,29(9):1063-1071
Previous studies in the wetland macrophyte Bidens laevis L have demonstrated that the insecticide endosulfan induces a high frequency of somatic chromosome aberrations in anaphase–telophase (CAAT) but no DNA changes as determined by the single cell gel electrophoresis (Comet) assay. Thus, cytogenetic biomarkers appear to be more sensitive to the toxic effects of the insecticide than the DNA molecule in the studied species. For this reason, the goals of this study were to use cytogenetic biomarkers—CAAT and abnormal metaphase—and defense biomarkers such as the activity of the antioxidant enzymes—guaiacol peroxidases (POD), glutathione reductase, and microsomal and cytosolic (m‐ and c‐) glutathione‐S‐transferase (GST)—to evaluate in B. laevis effects caused by a commercial formulation of endosulfan. The frequency of CAAT was increased at 5, 10, 50, and 100 μg/L endosulfan with respect to the negative controls by 3.1, 2.5, 2.5, and 3.2‐fold, respectively while the frequency of abnormal metaphases was also increased at the same concentrations by 3.5, 2.8, 3.2, and 11.3‐fold, respectively. In addition to these aneugenic effects, other abnormalities such as C‐mitosis and chromosome clumping were observed at 10 μg/L endosulfan. On the other hand, POD induction at 0.02, 0.5, 5, and 10 μg/L and m‐GST inhibition at 0.5, 10, and 50 μg/L in plants exposed during 24 h to endosulfan were observed but all of these responses were highly variable. In conclusion, only cytogenetic biomarkers like CAAT in B. laevis can serve potentially as early warning systems to detect environmentally relevant concentrations of endosulfan in aquatic ecosystems. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 1063–1071, 2014. 相似文献
42.
Sonia Zouaoui Amélie Darlix Pascale Fabbro-Peray Hélène Mathieu-Daudé Valérie Rigau Michel Fabbro Faiza Bessaoud Luc Taillandier François Ducray Fabienne Bauchet Michel Wager Thierry Faillot Laurent Capelle Hugues Loiseau Christine Kerr Philippe Menei Hugues Duffau Dominique Figarella-Branger Olivier Chinot Brigitte Trétarre Luc Bauchet 《Neurosurgical review》2014,37(3):415-424
The incidence of glioblastoma (GBM) has increased in patients aged 70 years or older, and will continue to grow. Elderly GBM patients have been excluded from most clinical trials; furthermore, optimal care management as well as benefit/risk ratio of GBM treatments are still being debated. This study describes oncological patterns of care, prognostic factors, and survival for patients ≥70 years in France. We identified patients over 70 with newly diagnosed and histologically confirmed GBM on data previously published by the French Brain Tumor DataBase. We included 265 patients. Neurological deficits and mental status disorders were the most frequent symptoms. The surgery consisted of resection (RS n?=?95) or biopsy (B n?=?170); 98 patients did not have subsequent oncological treatment. After surgery, first-line treatment consisted of radiotherapy (RT n?=?76), chemotherapy (CT n?=?52), and concomitant radiochemotherapy (CRC n?=?39). The median age at diagnosis was 76, 74, and 73 years, respectively, for the untreated, B?+?RT and/or CT, RS?±?RT and/or CT groups. Median survival (in days, 95 % CI) with these main strategies, when analyzed according to surgical groups, was: B-CT n?=?41, 199[155–280]; B-CRC n?=?21, 318[166–480]; B-RT n?=?37, 149[130–214]; RS-CT n?=?11, 245[211–na]; RS-CRC n?=?18, 372[349–593]; RS-RT n?=?39, 269[218–343]. This population study for elderly GBM patients is one of the most important in Europe, and could be considered as a historical cohort to compare future treatments. Moreover, we can hypothesize that elderly patients (versus patients <70 years) are undertreated. Karnofsky performance status seems to be the most relevant clinical predictive factor, and RS and CRC have a positive impact on survival for elderly GBM patients in the general population, at least when feasible. 相似文献
43.
Byung Sun Kim Junghee Lee Minji Bang Bo Am Seo Arshi Khalid Min Whan Jung Daejong Jeon 《Psychopharmacology》2014,231(22):4371-4381
Rationale
The aberrant regulation of serotonin (5-HT) and dopamine (DA) in the brain has been implicated in neuropsychiatric disorders associated with marked impairments in empathy, such as schizophrenia and autism. Many psychiatric drugs bind to both types of receptors, and the anterior cingulate cortex (ACC) is known to be centrally involved with empathy. However, the relationship between the 5-HT/DA system in the ACC and empathic behavior is not yet well known.Objectives
We investigated the role of 5-HT/DA in empathy-like behavior and in the regulation of ACC neural activity.Methods
An observational fear learning task was conducted following microinjections of 5-HT, DA, 5-HT and DA, methysergide (5-HT receptor antagonist), SCH-23390 (DA D1 receptor antagonist), or haloperidol (DA D2 receptor antagonist) into the mouse ACC. The ACC neural activity influenced by 5-HT and DA was electrophysiologically characterized in vitro and in vivo.Results
The microinjection of haloperidol, but not methysergide or SCH-23390, decreased the fear response of observing mice. The administration of 5-HT and 5-HT and DA together, but not DA alone, reduced the freezing response of observing mice. 5-HT enhanced delta-band activity and reduced alpha- and gamma-band activities in the ACC, whereas DA reduced only alpha-band activity. Based on entropy, reduced complexity of ACC neural activity was observed with 5-HT treatment.Conclusions
The current results demonstrated that DA D2 receptors in the ACC are required for observational fear learning, whereas increased 5-HT levels disrupt observational fear and alter the regularity of ACC neural oscillations. 相似文献44.
José-Francisco Rocha Amílcar Falcão Ana Santos Roberto Pinto Nelson Lopes Teresa Nunes Lyndon C. Wright Manuel Vaz-da-Silva Patrício Soares-da-Silva 《European journal of clinical pharmacology》2014,70(9):1059-1071
Background and objectives
Opicapone is a novel third generation catechol-O-methyltransferase (COMT) inhibitor. The purpose of this study was to compare the levodopa pharmacokinetic profile throughout a day driven by the COMT inhibition either following repeated doses of opicapone or concomitant administration with entacapone.Methods
A randomized, double-blind, gender-balanced, parallel-group study was performed in 4 groups of 20 healthy subjects each. Four subjects in each group received placebo during the entire study. Sixteen subjects in one group received placebo once daily for 11 days and on day 12, 200 mg entacapone concomitantly with each levodopa/carbidopa dose (three times separated by a 5-h interval). Sixteen subjects in each of the remaining three groups received respectively 25, 50, and 75 mg opicapone once daily for 11 days and on day 12, placebo concomitantly with each levodopa/carbidopa dose.Results
Levodopa minimum plasma concentration (Cmin) for each levodopa/carbidopa dose and for the mean of all levodopa/carbidopa doses increased substantially with all active treatments (entacapone and opicapone) when compared to the control group (placebo), with values ranging from 1.7-fold (200 mg entacapone) to 3.3-fold (75 mg opicapone). No statistical difference was found for levodopa peak of systemic exposure (as assessed by maximum observed plasma concentration (Cmax)) between all active treatments and placebo. A significant increase in the levodopa extent of systemic exposure (as assessed by concentration-time curve (AUC)) occurred with all opicapone treatments in relation to placebo. No statistical difference was found for levodopa AUC when entacapone was compared to placebo. When compared to entacapone, both 50 and 75 mg opicapone presented a significant increase for the levodopa AUC. All active treatments significantly inhibited both peak (as assessed by Emax) and extent (as assessed by effect-time curve (AUEC)) of the COMT activity in relation to placebo. When compared to entacapone, all opicapone treatments significantly decreased the extent (AUEC) of the COMT activity due to a long-lasting and sustained effect. The tolerability profile was favorable for all active treatments.Conclusion
Opicapone, a novel third generation COMT inhibitor, when compared to entacapone, provides a superior response upon the bioavailability of levodopa associated to more pronounced, long-lasting, and sustained COMT inhibition. The tolerability profile was favorable. On the basis of the results presented in this study and along with the earlier pharmacology studies, it is anticipated that opicapone adjunct therapy at the dosages of 25 and 50 mg will provide an enhancement in levodopa availability that will translate into clinical benefit for Parkinson’s disease patients. 相似文献45.
46.
Michelle N. Valadão Érica R. Coimbra Michele C. Landemberger Tonicarlo R. Velasco Vera C. Terra Lauro Wichert-Ana Veriano Alexandre Jr. David Araújo Jr. Ricardo Guarnieri Vilma R. Martins Antônio Carlos Santos Américo C. Sakamoto Roger Walz 《Neurological sciences》2014,35(2):239-244
The cellular prion protein, encoded by Prnp gene, is involved in neuroprotection, neuroplasticity and neurodevelopment. The variant allele Valine at codon 129 of the Prnp was associated with decreased brain volume in healthy volunteers and schizophrenic patients. We investigate the association between the cerebellum volume and the presence of variant allele Valine at codon 129 of the Prnp gene in patients with mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS). The Prnp coding sequence was determined in 41 refractory MTLE-HS patients. The cerebellum volume corrected by the intracranial volume of patients with the normal Prnp genotypes was compared with that of patients presenting the variant alleles at codon 129. Twenty patients showed the Met129Met genotype, 16 showed Met129Val, and 5 had Val129Val. There were no association among clinical, demographic, electrophysiological, antiepileptic drugs used, and the presence of the Prnp variant alleles. The presence of Prnp variant allele at codon 129 was not associated with the analyzed cerebellum volume. Prnp variant alleles at codon 129 are not associated with cerebellum volume in patients with refractory MTLE-HS. 相似文献
47.
48.
49.
Sébastien Brot Hinda Smaoune Mina Youssef‐Issa Céline Malleval Claire Benetollo Roger Besançon Carole Auger Mahnaz Moradi‐Améli Jérôme Honnorat 《The European journal of neuroscience》2014,40(7):3010-3020
The collapsin response‐mediator proteins (CRMPs) are multifunctional proteins highly expressed during brain development but down‐regulated in the adult brain. They are involved in axon guidance and neurite outgrowth signalling. Among these, the intensively studied CRMP2 has been identified as an important actor in axon outgrowth, this activity being correlated with the reorganisation of cytoskeletal proteins via the phosphorylation state of CRMP2. Another member, CRMP5, restricts the growth‐promotional effects of CRMP2 by inhibiting dendrite outgrowth at early developmental stages. This inhibition occurs when CRMP5 binds to tubulin and the microtubule‐associated protein MAP2, but the role of CRMP5 phosphorylation is still unknown. Here, we have studied the role of CRMP5 phosphorylation by mutational analysis. Using non‐phosphorylatable truncated constructs of CRMP5 we have demonstrated that, among the four previously identified CRMP5 phosphorylation sites (T509, T514, T516 and S534), only the phosphorylation at T516 residue was needed for neurite outgrowth inhibition in PC12 cells and in cultured C57BL/6J mouse hippocampal neurons. Indeed, the expression of the CRMP5 non‐phosphorylated form induced a loss of function of CRMP5 and the mutant mimicking the phosphorylated form induced the growth inhibition function seen in wildtype CRMP5. The T516 phosphorylation was achieved by the glycogen synthase kinase‐3β (GSK‐3β), which can phosphorylate the wildtype protein but not the non‐phosphorylatable mutant. Furthermore, we have shown that T516 phosphorylation is essential for the tubulin‐binding property of CRMP5. Therefore, CRMP5‐induced growth inhibition is dependent on T516 phosphorylation through the GSK‐3β pathway. The findings provide new insights into the mechanisms underlying neurite outgrowth. 相似文献
50.
Marie Buttitta Catalina Iliescu Amélie Rousseau Alain Guerrien 《Quality of life research》2014,23(4):1117-1139