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81.
Fernanda C. Flores Wing Sin Chiu Ruy C.R. Beck Cristiane B. da Silva M. Begoña Delgado-Charro 《International journal of pharmaceutics》2018,535(1-2):237-244
This work investigated the impact of formulation including in vitro release profile, repeated dosing, and nail poration on the ex vivo nail delivery performance of antifungal formulations. Chitosan coated and uncoated tioconazole-loaded nanocapsules and a nano-based film-forming vehicle were assessed via in vitro release and in vitro permeation tests using an artificial membrane and human nail clippings, respectively. The later involved single and daily dosing experiments with intact and porated nails. Additional experiments with Nile Red-loaded formulations evaluated the depth of penetration of the fluorescent marker into the nail by laser scanning confocal microscopy. The nanocapsule formulations prolonged release of tioconazole for longer than the control solutions and this ability was related to an enhanced nail penetration of the drug. Further, the new film-forming formulation delivered its drug payload more efficiently than a marketed product. Daily dosing of the formulations doubled the amount of drug recovered from the nails. Porating the nails enhanced tioconazole delivery in single dose experiments only. The depth of penetration of Nile Red into the nails clippings ranged between 90–160?μm. This research suggests that ensuring prolonged release of a drug is fundamental to develop efficacious topical nail formulations. 相似文献
82.
Dario Carradori Claudia Balducci Francesca Re Davide Brambilla Benjamin Le Droumaguet Orfeu Flores Alice Gaudin Simona Mura Gianluigi Forloni Lara Ordoñez-Gutierrez Francisco Wandosell Massimo Masserini Patrick Couvreur Julien Nicolas Karine Andrieux 《Nanomedicine : nanotechnology, biology, and medicine》2018,14(2):609-618
Alzheimer's disease (AD) is a neurodegenerative disorder related, in part, to the accumulation of amyloid-β peptide (Aβ) and especially the Aβ peptide 1-42 (Aβ1-42). The aim of this study was to design nanocarriers able to: (i) interact with the Aβ1-42 in the blood and promote its elimination through the “sink effect” and (ii) correct the memory defect observed in AD-like transgenic mice. To do so, biodegradable, PEGylated nanoparticles were surface-functionalized with an antibody directed against Aβ1-42. Treatment of AD-like transgenic mice with anti-Aβ1-42-functionalized nanoparticles led to: (i) complete correction of the memory defect; (ii) significant reduction of the Aβ soluble peptide and its oligomer level in the brain and (iii) significant increase of the Aβ levels in plasma. This study represents the first example of Aβ1-42 monoclonal antibody-decorated nanoparticle-based therapy against AD leading to complete correction of the memory defect in an experimental model of AD. 相似文献
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Kristiansen JE Hendricks O Delvin T Butterworth TS Aagaard L Christensen JB Flores VC Keyzer H 《The Journal of antimicrobial chemotherapy》2007,59(6):1271-1279
Intracellular efflux pumps have been largely the research focus in multidrug-resistant (MDR) Gram-positive and Gram-negative microorganisms and parasites including cancers. However, drug efflux mechanisms other than pumps per se have been observed, supported by the effects of isomeric, non-antibiotic depressant (DPR), phenothiazines and thixenes, and antidepressant (ADPR) phenylpiperidine neurotropic drugs, alone or in combination with classical antimicrobials on MDR Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus pyogenes and Streptococcus pneumoniae. Of the non-antibiotics we investigated, the DPR l-thioridazine, trans-clopenthixol and isomers of phenylpiperidines NNC 20-4962 (isomer of femoxetine) and NNC 20-7052 (isomer of paroxetine) were potent antimicrobials with the least neurotropic activity, pointing to a possible general isomeric structure-activity relationship. These compounds may be regarded as new efflux inhibitors. Moreover, these isomers have considerably reduced, in some cases absent, neurotropism and reduced mammalian toxicity. This may alleviate concerns about adverse effects and therapeutic safety for infected patients in life-threatening situations where the non-antibiotic dosage would be in the lower, non-chronic dosage ranges generally prescribed for individuals with mild mental health problems. The results point to the prokaryotic and eukaryotic microorganisms' phospholipid/protein domain involvement of the cationic, amphiphilic, non-antibiotic DPR and ADPR, with the phospholipids being the initial sites attracting and concentrating the neurotropes to induce a form of suspended animation, followed by gross changes of cell wall and membrane structure, and thereby potentiating their destructive or immobilizing effects on various as yet only hinted at resistance and efflux mechanisms. Combination of appropriate isomeric non-antibiotic DPR and ADPR of low neurotropism and toxicity with conventional and classical antimicrobials promises early, new therapeutic strategies salutary against microbial resistance, resistance development, pathogenicity and virulence. 相似文献
86.
Self-administration of medication suggests that individuals are functionally and cognitively competent to manage their health care. Older adults take a significant number of medications (borderline polypharmacy) as well as an unaccounted for number of over-the-counter, as necessary, and herbal remedies. Assisted living residences, moving from a social to a more medical model, are responsible for the safety and well-being of their residents. In addition, the prospect of aging-in-place in the residence is increasingly associated with appropriate medical and medication management. Assisted living services in most states include assistance with medication, but the nature of the assistance varies widely, at times approaching what even a nonclinical observer would regard as medication administration. Although state assisted living regulations can be quite specific regarding medication storage, there are scant guidelines about the components of a thorough assessment as to whether a resident can safely self-administer his or her medications. This article discusses assessment criteria of self-medication ability, drawn from a variety of instruments. In keeping with assisted living nursing standards of practice, the assisted living nurse has a critical responsibility in assessment of this self-care ability. 相似文献
87.
Sazzad Hassan Yelena Karpova Anabel Flores Ralph D’Agostino Jr. Suzanne C. Danhauer Ashok Hemal George Kulik 《International urology and nephrology》2014,46(3):505-510
Purpose
In mouse models of prostate cancer, increased epinephrine levels accelerated tumor growth via the beta2-adrenoreceptor/PKA signaling pathway. It is unknown, however, whether men experience increased epinephrine levels sufficient to activate the beta2-adrenoreceptor/PKA pathway in the prostate gland. We measured epinephrine levels in blood samples collected immediately prior to prostate biopsies and measured phosphorylation of S133CREB (PKA site), S112BAD, T202/Y204ERK, and S473 Akt in prostate biopsy tissue samples.Methods
Tissue samples and 3 ml of blood were obtained from men (n = 20) recruited from the patients scheduled for prostate biopsies. Epinephrine levels were measured by ELISA. Proteins were extracted from biopsied tissue, and protein phosphorylation was measured by Western blotting with phospho-specific antibodies. Pearson and Spearman’s rank correlations were analyzed to assess relationships between blood epinephrine levels and phosphorylation of CREB, BAD, AKT, and ERK.Results
Epinephrine levels above 1 nM were detected in 5 of 20 patients. A strong positive correlation was observed between increased epinephrine levels and CREB phosphorylation. In contrast, no correlation was observed between epinephrine levels and phosphorylation of ERK, BAD, or AKT.Conclusion
Our results suggest that increased blood epinephrine levels activate the beta2-adrenoreceptor/PKA signaling pathway in human prostate glands. These results will inform future studies to examine whether beta2-selective blockers can inhibit activation of the epinephrine/ADRB2/PKA pathway in prostate tumors of men with increased epinephrine levels and explore the use of beta2-selective blockers as adjuvant therapy for prostate cancer. 相似文献88.
Israel Camacho‐Abrego Gullermina Tellez‐Merlo Angel I. Melo Antonio Rodríguez‐Moreno Linda Garcés Fidel De La Cruz Sergio Zamudio Gonzalo Flores 《Synapse (New York, N.Y.)》2014,68(3):114-126
Several studies in rodents have suggested the inactivation of the subthalamic nucleus (STN) as an alternative strategy to Parkinson's disease (PD) treatment. The STN is part of the basal ganglia and plays an important role in the motor function; however, recent data suggest that this structure has a critical role in the cognitive function of the limbic system. The STN receives direct projection from the prefrontal cortex (PFC), structure interconnected with the hippocampus and both structures send excitatory projections to the nucleus accumbens (NAcc). Here, we determined whether and which changes occurred 4 weeks after a STN lesion in the dendritic morphology of pyramidal neurons of the layers 3 and 5 of the PFC and basolateral amygdala, neurons of the ventral hippocampus, and the medium spiny neurons of the NAcc and caudate‐putamen. Dendritic morphology was measured using the Golgi‐Cox procedure followed by Sholl analysis. We also evaluated the effects of STN lesion on locomotor behavior assessed by an open field test, social interaction, acoustic startle response, prepulse inhibition, and locomotor activity induced by a novel environment and amphetamine. We found that STN damage induced a deficit in locomotion measured by open field test with neuronal hypertrophy in PFC (layer 5) and reduced spinogenesis in CA1 ventral hippocampus and PFC (layer 3). Taken together, these data suggest that the behavioral and morphological effects of STN lesion are, at least partially, mediated by limbic subregions with possible consequences for cognitive‐related behaviors observed in PD treatment. Synapse 68:114–126, 2014. © 2013 Wiley Periodicals, Inc. 相似文献
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90.
Cesar Homero Gutirrez‐Aguirre Dalila Marisol Alvarado‐Navarro Alain Palomares‐Leal Gerardo Mejía‐Jaramillo Rosario Salazar‐Riojas Andrs Gmez‐De Len Perla Rocío Colunga‐Pedraza Guillermo Sotomayor‐Duque Jos Carlos Jaime‐Prez Olga Graciela Cantú‐Rodríguez Luz del Carmen Tarín‐Arzaga Juan Antonio Flores‐Jimnez David Gmez‐Almaguer 《Transfusion》2019,59(12):3721-3726