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141.
César Ida C Byrro RM Cardoso FF Mundim IM Teixeira Lde S da Silva EP Gomes SA Bonfim RR Pianetti GA 《Journal of pharmaceutical and biomedical analysis》2011,56(5):1094-1100
A sensitive and simple method was developed for the quantitation of levodopa and its metabolite 3-O-methyldopa, in human plasma, after oral administration of tablet formulations containing levodopa (200 mg) and benserazide (50 mg). The analytes were extracted by a protein precipitation procedure, using carbidopa as an internal standard. A mobile phase consisting of 0.2% formic acid and acetonitrile (94:6, v/v) was used and chromatographic separation was achieved using ACE C18 column (50 mm × 4.6 mm i.d.; 5 μm particle size). Selected reaction monitoring was performed using the fragmentation transitions m/z 198 → m/z 107, m/z 212 → m/z 166 and m/z 227 → m/z 181 for levodopa, 3-O-methyldopa and carbidopa, respectively. Calibration curves were constructed over the range 50.0-6000.0 ng/mL for levodopa and 25.0-4000.0 ng/mL for 3-O-methyldopa. The method shown to be specific, precise, accurate and provided recovery rates higher than 85% for all analytes. No matrix effect was detected in the samples. The validated method was applied in a pharmacokinetic study with a levodopa/benserazide tablet formulation in healthy volunteers. 相似文献
142.
Nogueira JB Sena LC Quintans Jde S Almeida JR França AV Júnior LJ 《Journal of pharmacy practice》2012,25(1):85-88
This study sought to decribe, quantify, and classify any adverse reactions occurring in patients with chronic hepatitis C treated with peginterferon and ribavirin, as well as verify the occurrence of potential medication interactions. The most prevalent reactions were fatigue (84.8%), fever (83%), weight loss (80%), irritability (74%), and body pain (72%). Most of the reactions were classified as mild (95%), whereas 4.5% were classified as moderate and 0.4% as severe. Adverse reactions led to the rearrangement of therapy for 9 patients (20%), where there was a reduction in dose for 7 (15%), temporary interruption of treatment for 5 (11%), and permanent discontinuation for 3 patients (7%). A total of 11 potential medication interactions were identified in 9 patients (20%), with the most frequent between peginterferon-α2a and captopril (45%). Given the above, it is observed that the treatment of chronic hepatitis C is marked by several adverse reactions of varying severity, which can interfere with the patient's quality of life or in treatment compliance, and that can be aggravated by potential drug-drug interactions. 相似文献
143.
Nigeria is an African country where transmission of malaria occurs all year round and where most inhabitants use plants as remedies against parasitic diseases, including malaria. Some of such medicinal plants have their antimalarial efficacies already demonstrated experimentally, active compounds isolated and the mechanism of drug action suggested. Decoction of Cocos nucifera husk is used in the middle belt region of Nigeria as an antimalarial remedy. In our current studies, we tested extracts from husks of four varieties of C. nucifera, all collected in Brazil, where the plant fruit is popularly named 'coco'. The husks of coco mesti?o, amarelo, an?o and gigante collected in the Northeast of Brazil were used to prepare extracts at the Chemistry Department, Federal University of Alagoas (UFAL), which were then tested for their antiplasmodial activities, cytotoxicities and hemolytic activities in vitro. Only the hexane extract of coco mesti?o was active against the blood forms of Plasmodium falciparum human malaria parasite maintained in continuous culture. Most extracts presented selectivity indices of <10, while hexane extract of coco mesti?o had a selectivity index of 35, meaning that the extract is not toxic. The isolation of the active compounds from coco mesti?o husks has not yet been done. 相似文献
144.
Santiago Vilar Rave Harpaz Eugenio Uriarte Lourdes Santana Raul Rabadan Carol Friedman 《J Am Med Inform Assoc》2012,19(6):1066-1074
Background
Drug–drug interactions (DDIs) are responsible for many serious adverse events; their detection is crucial for patient safety but is very challenging. Currently, the US Food and Drug Administration and pharmaceutical companies are showing great interest in the development of improved tools for identifying DDIs.Methods
We present a new methodology applicable on a large scale that identifies novel DDIs based on molecular structural similarity to drugs involved in established DDIs. The underlying assumption is that if drug A and drug B interact to produce a specific biological effect, then drugs similar to drug A (or drug B) are likely to interact with drug B (or drug A) to produce the same effect. DrugBank was used as a resource for collecting 9454 established DDIs. The structural similarity of all pairs of drugs in DrugBank was computed to identify DDI candidates.Results
The methodology was evaluated using as a gold standard the interactions retrieved from the initial DrugBank database. Results demonstrated an overall sensitivity of 0.68, specificity of 0.96, and precision of 0.26. Additionally, the methodology was also evaluated in an independent test using the Micromedex/Drugdex database.Conclusion
The proposed methodology is simple, efficient, allows the investigation of large numbers of drugs, and helps highlight the etiology of DDI. A database of 58 403 predicted DDIs with structural evidence is provided as an open resource for investigators seeking to analyze DDIs. 相似文献145.
de Oliveira MG Marques RB de Santana MF Santos AB Brito FA Barreto EO De Sousa DP Almeida FR Badauê-Passos D Antoniolli AR Quintans-Júnior LJ 《Basic & clinical pharmacology & toxicology》2012,111(2):120-125
α‐Terpineol (TPN), a volatile monoterpene alcohol, is relatively non‐toxic and one of the major components of the essential oils of various plant species. In this study, we tested for the antihypernociceptive activity of TPN (25, 50 or 100 mg/kg, i.p.) in mice using mechanical models of hypernociception induced by carrageenan (CG, 300 μg/paw) and the involvement of important mediators of its cascade signalling, such as tumour necrosis factor‐α (TNF‐α, 100 pg/paw), prostaglandin E2 (PGE2, 100 ng/paw) or dopamine (DA, 30 μg/paw). We also investigated the anti‐inflammatory effect of TPN on the model of carrageenan‐induced pleurisy and the LPS‐induced nitrite production in murine macrophages. Pre‐systemic treatment with TPN (25, 50 or 100 mg/kg, i.p.) inhibited the development of mechanical hypernociception induced by CG or TNF‐α. A similar effect was also observed upon PGE2 and DA administration. In addition, TPN significantly inhibited the neutrophil influx in the pleurisy model. TPN (1, 10 and 100 μg/mL) also significantly reduced (p < 0.01) nitrite production in vitro. Our results provide information about the antinociceptive and anti‐inflammatory properties of TPN on mechanical hypernociception and suggest that this compound might be potentially interesting in the development of new clinically relevant drugs for the management of painful and/or inflammatory disease. 相似文献
146.
Baldeiras Inês Esteves Ribeiro Maria Helena Pacheco Paula Machado Álvaro Santana Isabel Cunha Luís Oliveira Catarina Resende 《Journal of neurology》2009,256(9):1540-1550
The clinical diagnosis of sporadic Creutzfeldt–Jakob disease (sCJD) is difficult, and reliable markers are highly desired.
In this work we assess the value of several cerebrospinal fluid (CSF) markers for sCJD diagnosis. Within the framework of
the Portuguese Epidemiological Surveillance Program for Human Prion Diseases, CSF samples from 71 patients with clinically
suspected sCJD, 30 definite sCJD and 41 non-CJD patients, were analysed for the presence of 14-3-3 protein. CSF levels of
tau (t-tau), and phosphorylated tau (p-tau181), S-100b and β amyloid (Aβ42) proteins were determined. The influence of clinical
and genetic characteristics on CSF markers sensitivity was also evaluated. Protein 14-3-3 was detected in 29/30 sCJD patients
and 9/41 non-CJD patients. Extremely elevated t-tau and S-100b protein levels were found in sCJD patients, while p-tau181
levels were only slightly elevated and Aβ42 showed no differences compared to controls. 14-3-3 was the most sensitive parameter
(97%), but its specificity was low (78%); sensitivity/specificity for other proteins were: S-100b—93/93%, t-tau—93/95%, with
maximum accuracy being obtained by a combination of tests (14-3-3 combined with either t-tau or S-100b, or combining S-100b
with t-tau/Aβ42 or p-tau/t-tau ratios). The sensitivity of 14-3-3, as well as of p-tau181/t-tau ratio, was decreased in younger
patients with long disease duration, with the PrP-2 isotype and MV genotype. Both 14-3-3, t-tau and S-100b are sensitive markers
for sCJD, but 14-3-3 specificity seems to be lower in this special clinical setting of rapidly progressing dementias. We propose
that in cases with a 14-3-3 weak positive result, or in young patients with long disease duration, a second CSF marker would
be valuable for the diagnosis of sCJD. 相似文献
147.
Jorge Berlanga‐Acosta Jorge Gavilondo‐Cowley Pedro López‐Saura Tania González‐López María D Castro‐Santana Ernesto López‐Mola Gerardo Guillén‐Nieto Luis Herrera‐Martinez 《International wound journal》2009,6(5):331-346
Chemotaxis, mitogenesis, motogenesis and cytoprotection are common cellular events involved in both tumourigenesis and tissue repair, which appear amplified upon growth factors exposure. Epidermal growth factor (EGF) promotes these events in epithelial and mesenchymal cells through the binding to a specific tyrosine kinase receptor. In experimental oncology settings, EGF does not initiate malignant transformation but exhibits ‘tumour promotion’. These observations have raised doubts on the clinical use of EGF despite solid demonstrations of efficacy in experimental conditions and clinical trials. The results of a Pubmed and Bioline investigation on EGF clinical uses and preclinical safety data are presented here. EGF topical administration has been used since 1989 to enhance the healing process of a variety of peripheral tissues wounds (16 clinical reports), as well as its intravenous, oral and rectal administration for gastrointestinal damages (11 clinical reports). EGF therapeutic efficacy and excellent tolerability seem demonstrated. Lack of long‐term adverse effects is highlighted in those studies with 6, 12 and 24 months of patients follow‐up. Although post‐treatment follow‐up may fall short for malignant growth, there are no reports on evidences linking EGF clinical use with cancer. A multicentre, nationwide survey in Cuba, 15 years after randomly using silver sulphadiazine with EGF or not in burn victims yielded that cancer incidence was comparable between EGF‐treated and control subjects and that such incidence rate does not differ from the age‐matched national incidence for those 15‐year period. All the animal species subjected to long‐term EGF systemic administration exhibit dose‐dependent and reversible epithelial organs hyperplasia with no changes in cells phenotypic differentiation. Histotypic pre‐malignant markers were not identified. The results emerged from co‐carcinogenesis studies and from transgenic mice over‐expressing EGF are conflicting and indicate that EGF overexposure, either innate or postnatal, may not be sufficient to transform cells. The ability of EGF to heal injured tissues in life‐threatening scenarios or to assist in preventing physical and social disability advocates for its clinical use under a rational medical risk/benefit balance. 相似文献
148.
Mendes DG Lauria-Pires L Nitz N Lozzi SP Nascimento RJ Monteiro PS Rebelo MM Rosa Ade C Santana JM Teixeira AR 《Tropical medicine & international health : TM & IH》2007,12(5):629-636
Lack of conservation of the Amazon tropical rainforest has imposed severe threats to its human population living in newly settled villages, resulting in outbreaks of some infectious diseases. We conducted a seroepidemiological survey of 1100 inhabitants of 15 villages of Paço do Lumiar County, Brazil. Thirty‐five (3%) individuals had been exposed to Trypanosoma cruzi (Tc), 41 (4%) to Leishmania braziliensis (Lb) and 50 (4.5%) to Leishmania chagasi (Lc) infections. Also, 35 cases had antibodies that were cross‐reactive against the heterologous kinetoplastid antigens. Amongst these, the Western blot assays revealed that 11 (1%) had Tc and Lb, that seven (0.6%) had Lc and Tc, and that 17 (1.6%) had Lb and Lc infections. All of these cases of exposures to mixed infections with Leishmania sp, and eight of 11 cases of Tc and Lb were confirmed by specific PCR assays and Southern hybridizations. Two cases had triple infections. We consider these asymptomatic cases showing phenotype and genotype markers consistent with mixed infections by two or more kinetoplastid flagellates a high risk factor for association with Psychodidae and Triatominae vectors blood feeding and transmitting these protozoa infections. This is the first publication showing human exposure to mixed asymptomatic kinetoplastid infections in the Amazon. 相似文献
149.
Antipsychotic drugs reverse the disruption in prefrontal cortex function produced by NMDA receptor blockade with phencyclidine 总被引:3,自引:0,他引:3
Kargieman L Santana N Mengod G Celada P Artigas F 《Proceedings of the National Academy of Sciences of the United States of America》2007,104(37):14843-14848
NMDA receptor (NMDA-R) antagonists are extensively used as schizophrenia models because of their ability to evoke positive and negative symptoms as well as cognitive deficits similar to those of the illness. Cognitive deficits in schizophrenia are associated with prefrontal cortex (PFC) abnormalities. These deficits are of particular interest because an early improvement in cognitive performance predicts a better long-term clinical outcome. Here, we examined the effect of the noncompetitive NMDA-R antagonist phencyclidine (PCP) on PFC function to understand the cellular and network elements involved in its schizomimetic actions. PCP induces a marked disruption of the activity of the PFC in the rat, increasing and decreasing the activity of 45% and 33% of the pyramidal neurons recorded, respectively (22% of the neurons were unaffected). Concurrently, PCP markedly reduced cortical synchrony in the delta frequency range (0.3-4 Hz) as assessed by recording local field potentials. The subsequent administration of the antipsychotic drugs haloperidol and clozapine reversed PCP effects on pyramidal cell firing and cortical synchronization. PCP increased c-fos expression in PFC pyramidal neurons, an effect prevented by the administration of clozapine. PCP also enhanced c-fos expression in the centromedial and mediodorsal (but not reticular) nuclei of the thalamus, suggesting the participation of enhanced thalamocortical excitatory inputs. These results shed light on the involvement of PFC in the schizomimetic action of NMDA-R antagonists and show that antipsychotic drugs may partly exert their therapeutic effect by normalizing a disrupted PFC activity, an effect that may add to subcortical dopamine receptor blockade. 相似文献
150.