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《Journal of pharmaceutical sciences》2019,108(10):3425-3433
This study aimed at evaluating how encapsulation in a regular nanocarrier (NC) (providing extended circulation time) or in a brain-targeting NC (providing prolonged circulation time and increased brain uptake) may influence the therapeutic index compared with the unformulated drug and to explore the key parameters affecting therapeutic performance using a model-based approach. Pharmacokinetic (PK) models were built with chosen PK parameters. For a scenario where central effect depends on area under the unbound brain concentration curve and peripheral toxicity relates to peak unbound plasma concentration, dose-effect and drug-side effect curves were constructed, and the therapeutic index was evaluated. Regular NC improved the therapeutic index compared with the unformulated drug due to reduced peripheral toxicity, while brain-targeting NC enhanced the therapeutic index by lowering peripheral toxicity and increasing central effect. Decreasing drug release rate or systemic clearance of NC with drug still encapsulated could increase the therapeutic index. Also, a drug with shorter half-life would therapeutically benefit more from a NC encapsulation. This work provides insights into how a NC for brain delivery should be optimized to maximize the therapeutic performance and is helpful to predict if and to what extent a drug with certain PK properties would obtain therapeutic benefit from nanoencapsulation. 相似文献
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《Journal of hand therapy》2020,33(4):528-539
Study DesignProspective longitudinal cohort study.IntroductionTraumatic brachial plexus injuries (BPIs) can be devastating and negatively impact daily function and quality of life. Occupational therapists play an important role in rehabilitation; however, studies identifying outcomes are lacking.PurposeThis study aims to describe outcomes including motor recovery, upper limb function, participation, pain, and quality of life for people receiving occupational therapy intervention.MethodsA convenience sample of English-speaking adults (n = 30) with a traumatic BPI, attending the clinic between December 1, 2014, to November 30, 2016, participated. Participants received occupational therapy focusing on sensorimotor retraining and activity-based rehabilitation. Data on active range of motion (goniometry), strength (Medical Research Council (MRC)), upper-limb function (UEFI15, QuickDASH), participation (PSFS), pain (Brief Pain Inventory), and quality of life (EQ-5D-3L) were collected at baseline, 3, 6, 9, and 12 months.ResultsElbow flexion strength showed significant improvement at all time-points, average increase 2.17 (MRC) (95% confidence interval: 1.29-3.04; P < .001) and mean final MRC grading 3.86 (standard error: 0.44). Significant improvements at 12 months were seen in: shoulder abduction strength and range, flexion strength and range, external rotation range; elbow extension strength and flexion range; thumb flexion and extension strength. Upper limb function (QuickDASH) showed significant improvement (mean change = 18.85; 95% confidence interval: 4.12-33.59; P = .02). Forearm protonation range and finger flexion strength were significantly worse. Remaining outcomes did not show significant improvement.ConclusionsOccupational therapy with surgical intervention can improve strength, range, and upper limb function with people following traumatic BPI. Further investigations into impact on participation, pain, and quality of life are required. 相似文献
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IntroductionCentral venous catheter applications and complications are closely related to the tip position. Previous studies have reported some rare cases of catheter misplacement. Here, we report a case of misplacement of a peripherally inserted central catheter into the lateral thoracic vein.Case reportA 56-year-old cancer patient underwent placement of a peripherally inserted central catheter through the left basilic vein under ultrasound-guided puncture. The catheterisation procedure was uneventful, so the catheter was believed to be in the superior vena cava. However, the post-anterior chest X-ray image revealed that after the catheter advanced towards the axilla, it turned downwards and outwards in the direction of the left lateral thoracic region, with the projection of the catheter tip giving the appearance of termination in the subcutaneous tissue of the lateral thoracic wall on the two-dimensional image. The catheter was then repositioned in the distal superior vena cava.DiscussionPeripherally inserted central catheters can be potentially misplaced into the lateral thoracic vein because these catheters can pass through the orifice of the lateral thoracic vein which flows into the axillary vein. Some pathological cases and clinical conditions can cause dilatation of the lateral thoracic vein, which increases the probability of catheter misplacement. Three principles were proposed to avoid this rare complication: a comprehensive review of the patients’ medical history, real-time image-guided catheterisation and routine radiographic identification of the tip position. 相似文献
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上肢骨肿瘤切除后的自体骨移植重建 总被引:1,自引:0,他引:1
目的探讨应用自体骨移植对上肢骨肿瘤切除后的骨缺损修复重建的效果。方法1998年8月~2004年3月,收治上肢骨肿瘤切除后的骨缺损16例。男8例,女8例。年龄7~45岁。经病理确诊,肱骨近端尤文肉瘤和骨肉瘤各1例;肱骨远端尤文肉瘤2例;桡骨远端骨巨细胞瘤8例,高分化软骨肉瘤2例,恶性纤维组织细胞瘤和骨肉瘤各1例。2例肱骨近端肿瘤行自体锁骨代肱骨;2例肱骨远端肿瘤行自体腓骨代肱骨;12例桡骨远端肿瘤中,1例行自体髂骨移植,11例行自体腓骨代桡骨进行重建。采用MSTS系统进行术后功能评价。结果2例肱骨近端自体锁骨移植患者分别随访36个月和12个月,术后保持部分肩关节前屈和后伸功能,但外展功能丧失;MSTS评分分别为23分和22分。2例肱骨远端自体腓骨移植患者分别随访4个月和6个月,肘关节功能良好,移植骨连接处已经出现骨愈合;MSTS功能评分分别为24分和19分。12例桡骨远端自体骨移植患者中11例随访6~75个月,功能良好,无明显并发症;1例髂骨植骨的桡骨远端骨巨细胞瘤术后3个月移植骨完全愈合,至今随访75个月,肿瘤无复发。MSTS功能评分18~27分,平均22.6分。结论自体骨移植在上肢骨肿瘤切除后骨缺损的重建,尤其是儿童的骨缺损重建中,是一种较好的方法。 相似文献
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Mhamed 《Computerized medical imaging and graphics》2006,30(8):447-451
The aim in this work is to report a new method to calculate parametric images from a single scan acquisition with positron emission tomography (PET) and fluorodeoxyglucose (FDG) in the human brain without blood sampling. It is usually practical for research or clinical purposes to inject the patient in an isolated room and to start the PET acquisition only for some 10–20 min, about 30 min after FDG injection. In order to calculate the cerebral metabolic rates for glucose (CMRG), usually several blood samples are required. The proposed method considers the relation between the uptake of the tracer in the cerebellum as a reference tissue and the population based input curve. Similar results were obtained for CMRG values with the present method in comparison to the usual autoradiographic and the non-linear least squares fitting of regions of interest. 相似文献