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101.
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Synthesis of Novel Pyrimidin‐4‐One Bearing Piperazine Ring‐Based Amides as Glycogen Synthase Kinase‐3β Inhibitors with Antidepressant Activity 下载免费PDF全文
Imran Khan Mushtaq A. Tantray Hinna Hamid Mohammad Sarwar Alam Abul Kalam Faraz Shaikh Anamik Shah Firasat Hussain 《Chemical biology & drug design》2016,87(5):764-772
Novel pyrimidin‐4‐one derivatives have been synthesized using EDC coupling and evaluated as glycogen synthase kinase‐3β (GSK‐3β) inhibitors. Among all the synthesized compounds, compound 5 (3‐methyl‐6‐phenyl‐2‐(piperazin‐1‐yl)‐3,4‐dihydropyrimidin‐4‐one) exhibited the most potent inhibitory activity against GSK‐3β with IC50 value of 74 nm . The molecular docking studies were performed to elucidate the binding modes of the compounds with the target, and a crucial interaction involving hydrogen bond formation with Val‐135 to the active site of GSK‐3β was observed. Furthermore, the synthesized compounds were subjected to in vivo evaluation of their antidepressant activity, and compound 5 showing highest inhibition of GSK‐3β was also found to significantly reduce the duration of immobility at 50 mg/kg, when compared with fluoxetine, a known antidepressant drug. The results of our study suggest that compound 5 may serve as a valuable template for the design and development of inhibitors of GSK‐3β with antidepressant activity. 相似文献
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Soofi SB Habib MA von Seidlein L Khan MJ Muhammad S Bhutto N Khan MI Rasool S Zafar A Clemens JD Nizami Q Bhutta ZA 《Journal of infection and public health》2011,4(1):12-21
Despite the efforts of the international community diarrheal diseases still pose a major threat to children in children less than five years of age. Bacterial diarrhea has also emerged as a public health concern due to the proliferation of drug resistant species in many parts of the world. There is a paucity of population-based data about the incidence of shigellosis and Campylobacter infections in Pakistan. We report country specific results for Shigella diarrhea that were derived from a multicenter study conducted in six Asian countries. Disease surveillance was conducted over a 24 month period in urban slums of Karachi, Pakistan, a city with a population of 59,584. Cases were detected through passive detection in study treatment centers. Stool specimens or rectal swabs were collected from all consenting patients. Between January 2002 and December 2003 10,540 enteric infection cases were detected. The incidence rate of treated diarrhea in children under 5 was 488/1000/year. In children, 5 years and older, the diarrhea rate was 22/1000/year. 576 (7%) Campylobacter isolates were detected. The pre-dominant Campylobacter species was C. jenuni with an increase of 29/1000 year in children under 5 years. Shigella species were isolated from 394 of 8032 children under 5 years of age. Shigella flexneri was the dominant species (10/1000/year in children under 5 years) followed by Shigella sonnei (3.9/1000/year), Shigella boydii (2.0/1000/year) and Shigella dysenteriae (1.3/1000/year). Shigellosis and Campylobacter infection rates peaked during the second year of life. The incidence rate of shigellosis increased in old age but such a trend was not observed in Campylobacter infections. Of 394 shigellosis patients 123 (31%) presented with dysentery in contrast to only 54 (9%) of 576 patients with Campylobacter infections (p<0.001). Both Campylobacter infections and shigellosis are common in community settings of Pakistan but shigellosis presented more frequently with abdominal pain and dysentery than Campylobacter infections indicating that shigellosis may be a more severe illness than Campylobacter infections. Due to the increased and disease severity, drug resistant shigella have become a significant health problem; moreover it is a disease of poor and impoverished people who do not have the access to standard water and sanitary conditions, health care services or optimal treatment. In the face of these facts it is empirically important to develop a low cost effective vaccine that can protect these populations for a longer duration. 相似文献
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ObjectiveTo compare the attitudes of preclinical and clinical dental students toward their own oral health using the Hiroshima University-Dental Behavioral Inventory (HU-DBI).MethodsThe English-language version of the 20-item HU-DBI was distributed to all preclinical and clinical students at the College of Dentistry, University of Dammam, Kingdom of Saudi Arabia. Dichotomized (agree/disagree) responses to 12 HU-DBI items were used in this study, with a maximum possible score of 12. Responses to the remaining eight statements reflected general oral health attitudes and were excluded from the analysis. Data were analyzed statistically.ResultsThe overall response rate was 72.2% (preclinical, 72.5%; clinical, 72%). The mean HU-DBI score was significantly higher among clinical than among preclinical dental students (7 vs. 5.8; P < 0.05). Higher proportions of preclinical than clinical students did not worry about visiting the dentist but postponed dental visits until they experienced toothache. Furthermore, more preclinical than clinical students reported that their gums bled upon brushing, used a child-sized toothbrush, had observed white, sticky deposits on their teeth, and used strong strokes for toothbrushing. More clinical than preclinical students reported that they did not feel that the condition of their teeth was worsening despite brushing, worried about the color of their teeth, brushed each of their teeth carefully, and checked their teeth in the mirror after brushing.ConclusionsDental health awareness programs should be implemented and information about positive oral health attitudes should be provided to the students at an initial stage of dental training. 相似文献
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Syed Imran A. RizviDavid A. Waller 《Surgery (Oxford)》2011,29(5):217-220
Early recognition of empyema is of prime importance. Accurate assessment of stage is crucial in planning management. Exudative empyema (stage I) should be treated by aspiration or tube thoracostomy. Fibrinopurulent empyema (stage II) can be treated effectively by video-assisted thoracic surgery (VATS). Debridement and decortication are the main components of surgical treatment of stage III empyema. It is worthwhile assessing most cases by video-assisted thoracoscopy. 相似文献
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Imran SaeedJon Anderson 《Surgery (Oxford)》2011,29(5):221-226
Primary lung cancer is the leading cause of cancer-related deaths in industrialized countries. Despite advances in treatment, the overall 5-year survival remains poor due to the advanced stage of disease at presentation. Smoking remains the main risk factor being responsible for around 85% of all cases. The most important distinction is that between non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Surgeons primarily deal with NSCLC (SCLC is an aggressive tumour that usually presents with systemic disease). NSCLC has a number of histological subtypes.Patient evaluation aims to establish the cell type of the tumour, determine the stage of the disease, and to determine fitness for surgery. Staging of NSCLC is based on the tumour/node/metastasis (TNM) classification. Procedures used to diagnose or stage lung cancer can include chest X-ray, chest computed tomography (CT) scan, combined positron emission tomography/CT, CT or transbronchial guided needle biopsy, and mediastinoscopy amongst others. Surgery is the only established method for ‘curing’ NSCLC. However, only a quarter of patients have resectable disease at presentation. Surgical resection can be performed using a variety of procedures including lobectomy, pneumonectomy or wedge resections. The 5-year survival of patients with stage I lung cancer following surgical resection is 51-60%. 相似文献
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