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131.
Camille G. Apple Elizabeth S. Miller Kolenkode B. Kannan Julie A. Stortz Tyler J. Loftus Maria Cecilia Lopez Hari K. Parvataneni Matthew Patrick Jennifer E. Hagen Henry V. Baker Philip A. Efron Alicia M. Mohr 《Surgery》2021,169(5):1206-1212
BackgroundPrevious data has shown that severe traumatic injury is associated with bone marrow dysfunction, which manifests as persistent injury-associated anemia. This study sought to identify whether the expression of erythropoiesis-related microRNAs were altered in the bone marrow of trauma patients to determine if these microRNAs play a role in persistent injury-associated anemia.MethodsBone marrow was collected from severely injured trauma patients who underwent fracture fixation as well as patients who underwent elective hip replacement. There were 27 trauma patients and 10 controls analyzed. Total RNA and microRNA were isolated from CD34-positive cells using the RNeasy Plus Mini kit, and genome-wide microRNA expression patterns were assayed. Genes with significant expression differences were found using BRB-ArrayTools with a significance of P < .01.ResultsThere were marked differences in expression of 108 microRNAs in the trauma group when compared with hip replacement patients. Four of these microRNAs play a role in regulating erythropoiesis: microRNA-150, microRNA-223, microRNA15a, and microRNA-24. These microRNAs were all upregulated significantly, with trauma/hip replacement fold changes of 1.7, 1.8, 1.2, and 1.2 respectively, and all act to suppress or regulate erythropoiesis.ConclusionAssessment of the bone marrow microRNA profile in trauma patients compared to those undergoing elective hip replacement revealed the differential expression of microRNA-150, microRNA-223, microRNA-15a, and microRNA-24. These microRNAs all play a role in decreased erythroid progenitor cell growth and provide important insight to the erythropoietic dysfunction seen after trauma. 相似文献
132.
Suzanne M Jan de Beur Paul D Miller Thomas J Weber Munro Peacock Karl Insogna Rajiv Kumar Frank Rauch Diana Luca Tricia Cimms Mary Scott Roberts Javier San Martin Thomas O Carpenter 《Journal of bone and mineral research》2021,36(4):627-635
Tumor-induced osteomalacia (TIO) is caused by phosphaturic mesenchymal tumors producing fibroblast growth factor 23 (FGF23) and is characterized by impaired phosphate metabolism, skeletal health, and quality of life. UX023T-CL201 is an ongoing, open-label, phase 2 study investigating the safety and efficacy of burosumab, a fully human monoclonal antibody that inhibits FGF23, in adults with TIO or cutaneous skeletal hypophosphatemia syndrome (CSHS). Key endpoints were changes in serum phosphorus and osteomalacia assessed by transiliac bone biopsies at week 48. This report focuses on 14 patients with TIO, excluding two diagnosed with X-linked hypophosphatemia post-enrollment and one with CSHS. Serum phosphorus increased from baseline (0.52 mmol/L) and was maintained after dose titration from week 22 (0.91 mmol/L) to week 144 (0.82 mmol/L, p < 0.0001). Most measures of osteomalacia were improved at week 48: osteoid volume/bone, osteoid thickness, and mineralization lag time decreased; osteoid surface/bone surface showed no change. Of 249 fractures/pseudofractures detected across 14 patients at baseline, 33% were fully healed and 13% were partially healed at week 144. Patients reported a reduction in pain and fatigue and an increase in physical health. Two patients discontinued: one to treat an adverse event (AE) of neoplasm progression and one failed to meet dosing criteria (receiving minimal burosumab). Sixteen serious AEs occurred in seven patients, and there was one death; all serious AEs were considered unrelated to treatment. Nine patients had 16 treatment-related AEs; all were mild to moderate in severity. In adults with TIO, burosumab exhibited an acceptable safety profile and was associated with improvements in phosphate metabolism and osteomalacia. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.. 相似文献
133.
Sohrab Virk Kathleen N. Meyers Virginie Lafage Suzanne A. Maher Tony Chen 《The spine journal》2021,21(4):698-707
Background ContextAnnular repair devices offer a solution to recurrent disc herniations by closing an annular defect and lowering the risk of reherniation. Given the significant risk of neurologic injury from device failure it is imperative that a reliable preclinical model exists to demonstrate a high load to failure for the disc repair devices.PurposeTo establish a preclinical model for disc herniation and demonstrate how changes in species, intervertebral disc height and Pfirrmann classification impacts failure load on an injured disc. We hypothesized that: (1) The force required for disc herniation would be variable across disc morphologies and species, and (2) for human discs the force to herniation would inversely correlate with the degree of disc degeneration.Study designAnimal and human cadaveric biomechanical model of disc herniation.MethodsWe tested calf lumbar spines, bovine tail segments and human lumbar spines. We first divided individual lumbar or tail segments to include the vertebral bodies and disc. We then hydrated the specimens by placing them in a saline bath overnight. A magnetic resonance images were acquired from human specimens and a Pfirrmann classification was made. A stab incision measuring 25% of the diameter of the disc was then done to each specimen along the posterior intervertebral disc space. Each specimen was placed in custom test fixtures on a servo-hydraulic test frame (MTS, Eden Prarie, MN) such that the superior body was attached to a 10,000 lb load cell and the inferior body was supported on the piston. A compressive ramping load was placed on the specimen in load control at 4 MPa/sec stopping at 75% of the disc height. Load was recorded throughout the test and failure load calculated. Once the test was completed each specimen was sliced through the center of the disc and photos were taken of the cut surface.ResultsFifteen each of calf, human, and bovine tail segments were tested. The failure load varied significantly between specimens (p<.001) with human specimens having the highest average failure load (8154±2049 N). Disc height was higher for lumbar/bovine tail segments as compared to calf specimens (p<.001) with bovine tails having the highest disc height (7.1±1.7 mm). Similarly, human lumbar discs had a cross sectional area that was greater than both bovine tail/calf lumbar spines (p<.001). There was no correlation between disc height and failure load within each individual species (p>.05). Cross sectional area and failure load did not correlate with failure load for human lumbar spine and bovine tails (p>.05) but did correlate with calf spine (r=0.53, p=.04). There was a statistically significant inverse correlation between disc height and Pfirrmann classification for human lumbar spines (r=?0.84, p<.001). There was also a statistically significant inverse relationship between Pfirrmann classification and failure load (r=?0.58, p=.02).ConclusionsWe have established a model for disc herniation and have shown how results of this model vary between species, disc morphology, and Pfirrmann classification. Both hypotheses were accepted: The force required for disc herniation was variable across species, and the force to herniation for human spines was inversely correlated with the degree of disc degeneration. We recommend that models using human intervertebral discs should include data on Pfirrmann classification, while biomechanical models using calf spines should report cross sectional area. Failure loads do not vary based on dimensions for bovine tails.Clinical SignificanceOur analysis of models for disc herniation will allow for quicker, reliable comparisons of failure forces required to induce a disc herniation. Future work with these models may facilitate rapid testing of devices to repair a torn/ruptured annulus. 相似文献
134.
Suzanne R. Sharpton Norah A. Terrault Mehdi M. Tavakol Andrew M. Posselt 《American journal of transplantation》2021,21(10):3324-3332
Strategies to optimize the management of obesity-related metabolic complications after liver transplantation (LT) are needed. We examined the effect of pre-LT sleeve gastrectomy (SG), as compared to medical weight loss (MWL), on post-LT outcomes. This is a cohort study of adults (≥18 years) with medically complicated obesity who were eligible for pre-LT SG and underwent LT from January 1, 2006 to June 1, 2016. Logistic regression models evaluated the association of SG on post-LT diabetes and hypertension, defined as new-onset or progressive disease post-LT. Cox regression models evaluated the association of SG on recurrent and de novo nonalcoholic fatty liver disease (NAFLD). Among 70 LT recipients who were eligible for pre-LT SG, 14 (20%) underwent SG and 56 (80%) underwent MWL only. Mean follow-up was 5.2 years post-LT. The SG cohort sustained higher % total body weight loss at 3 years post-LT (28.9% vs. 5.4%, p < .001). In multivariable analyses, SG was associated with significantly lower risk of post-LT diabetes (OR 0.04, 95% CI 0.00–0.41, p = .01), hypertension (OR 0.15, 95% CI 0.04–0.67, p = .01), and recurrent and de novo NAFLD (HR 0.19, 95% CI 0.04–0.91, p = .04). When compared to MWL, SG resulted in sustained weight loss and significantly lower risk of diabetes, hypertension, and recurrent and de novo NAFLD post-LT. 相似文献
135.
Xiao Xu Pamela R. Soulos Jeph Herrin ShiYi Wang Craig Evan Pollack Suzanne B. Evans James B. Yu Cary P. Gross 《Health services research》2021,56(3):497
ObjectiveTo examine variation in trajectories of abandoning conventionally fractionated whole‐breast irradiation (CF‐WBI) for adjuvant breast radiotherapy among physician peer groups and the associated cost implications.Data SourcesMedicare claims data were obtained from the Chronic Conditions Data Warehouse for fee‐for‐service beneficiaries with breast cancer in 2011‐2014.Study DesignWe used social network methods to identify peer groups of physicians that shared patients. For each physician peer group in each time period (T1 = 2011‐2012 and T2 = 2013‐2014), we calculated a risk‐adjusted rate of CF‐WBI use among eligible women, after adjusting for patient clinical characteristics. We applied a latent class growth analysis to these risk‐adjusted rates to identify distinct trajectories of CF‐WBI use among physician peer groups. We further estimated potential savings to the Medicare program by accelerating abandonment of CF‐WBI in T2 using a simulation model.Data Collection/Extraction MethodsUse of conventionally fractionated whole‐breast irradiation was determined from Medicare claims among women ≥ 66 years of age who underwent adjuvant radiotherapy after breast conserving surgery.Principal FindingsAmong 215 physician peer groups caring for 16 988 patients, there were four distinct trajectories of abandoning CF‐WBI: (a) persistent high use (mean risk‐adjusted utilization rate: T1 = 94.3%, T2 = 90.6%); (b) decreased high use (T1 = 81.3%, T2 = 65.3%); (c) decreased medium use (T1 = 60.1%, T2 = 44.0%); and (d) decreased low use (T1 = 31.6%, T2 = 23.6%). Peer groups with a smaller proportion of patients treated at free‐standing radiation facilities and a larger proportion of physicians that were surgeons tended to follow trajectories with lower use of CF‐WBI. If all physician peer groups had practice patterns in T2 similar to those in the “decreased low use” trajectory, the Medicare program could save $83.3 million (95% confidence interval: $58.5 million‐$112.2 million).ConclusionsPhysician peer groups had distinct trajectories of abandoning CF‐WBI. Physician composition and setting of radiotherapy were associated with the different trajectories. Distinct practice patterns across the trajectories had important cost implications. 相似文献
136.
Skevington Suzanne M. Rowland Christine Panagioti Maria Bower Peter Krägeloh Christian 《Quality of life research》2021,30(3):891-903
Quality of Life Research - We revisited the global concept of subjective quality of life (QoL) as assessed by the WHOQOL-BREF to investigate whether it could be elaborated into a conceptually more... 相似文献
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139.
Finkelman FD Rothenberg ME Brandt EB Morris SC Strait RT 《The Journal of allergy and clinical immunology》2005,115(3):449-57; quiz 458
Studies with murine models demonstrate 2 pathways of systemic anaphylaxis: one mediated by IgE, Fc epsilonRI, mast cells, histamine, and platelet-activating factor (PAF), and the other mediated by IgG, Fc gammaRIII, macrophages, and PAF. The former pathway requires much less antibody and antigen than the latter. As a result, IgG antibody can block IgE-mediated anaphylaxis induced by small quantities of antigen without mediating Fc gammaRIII-dependent anaphylaxis. The IgE pathway is most likely responsible for most human anaphylaxis, which generally involves small amounts of antibody and antigen; similarities in the murine and human immune systems suggest that the IgG pathway might mediate disease in persons repeatedly exposed to large quantities of antigen. Mice, like human subjects, can experience IgE/Fc epsilonRI/mast cell-mediated gastrointestinal and systemic anaphylaxis in response to ingested antigen. Gastrointestinal symptoms depend on serotonin and PAF; mediator dependence of systemic symptoms has not been determined. Both local and systemic anaphylaxis induced by ingested antigens might be blocked by IgA and IgG antibodies. IL-4 and IL-13 signaling through the IL-4 receptor alpha chain, in addition to promoting the mastocytosis and IgE antibody production that mediate most human anaphylaxis, exacerbates the effector phase of anaphylaxis by increasing target cell responsiveness to vasoactive mediators. As a result, IL-4 receptor alpha chain antagonists might be particularly effective suppressors of anaphylaxis. 相似文献
140.
Laurie H. Seaver Suzanne B. Cassidy 《American journal of medical genetics. Part A》1991,41(4):405-409
We report on a mother and son with a similar syndrome of hypertelorism and telecanthus, epicanthal folds, downslanting palpebral fissures, ptosis, broad nasal bridge, malar hypoplasia, thin upper lip, smooth philtrum, and apparently low-set prominent ears. The son also has a hypoplastic shawl scrotum, cryptorchidism, and genu valgum. His language development was delayed at 18 months, but subsequently improved and was normal at age 3. The mother has the additional findings of marked cubitus valgus, hyperextensible joints, dull normal intelligence and a bleeding diathesis. This pattern of multiple congenital anomalies may represent a new syndrome. 相似文献