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排序方式: 共有2347条查询结果,搜索用时 15 毫秒
71.
Olivera Grbovic-Huezo Kenneth L. Pitter Nicolas Lecomte Joseph Saglimbeni Gokce Askan Matilda Holm Jerry P. Melchor Rohit Chandwani Suhasini Joshi Caj Haglund Christine A. Iacobuzio-Donahue Gabriela Chiosis Tuomas Tammela Steven D. Leach 《Proceedings of the National Academy of Sciences of the United States of America》2020,117(48):30670
72.
Isabelle Traini Jessica Menzies Jennifer Hughes Steven Thomas Leach Usha Krishnan 《World journal of gastroenterology : WJG》2020,26(12):1262-1272
Poor growth is an under-recognised yet significant long-term sequelae of oesophageal atresia(OA) repair. Few studies have specifically explored the reasons for growth impairment in this complex cohort. The association between poor growth with younger age and fundoplication appears to have the strongest supportive evidence, highlighting the need for early involvement of a dietitian and speech pathologist, and consideration of optimal medical reflux management prior to referring for anti-reflux surgery. However, it remains difficult to reach conclusions regarding other factors which may negatively influence growth, due to conflicting findings, inconsistent definitions and lack of validated tool utilisation. While swallowing and feeding difficulties are particularly frequent in younger children, their relationship with growth remains unclear. It is possible that these morbidities impact on the diet of children with OA, but detailed analysis of dietary composition and quality, and its relationship with these complications and growth, has not yet been conducted. Another potential area of research in OA is the role of the microbiota in growth and nutrition. While the microbiota has been linked to growth impairment in other paediatric conditions,it is yet to be investigated in OA. Further research is needed to identify the most,important contributory factors to poor growth, the role of the intestinal microbiota, and effective interventions to maximise growth and nutritional outcomes in this cohort. 相似文献
73.
Positive and negative allosteric modulators promote biased signaling at the calcium-sensing receptor
Davey AE Leach K Valant C Conigrave AD Sexton PM Christopoulos A 《Endocrinology》2012,153(3):1232-1241
The calcium-sensing receptor (CaSR) is a G protein-coupled receptor whose function can be allosterically modulated in a positive or negative manner by calcimimetics or calcilytics, respectively. Indeed, the second-generation calcimimetic, cinacalcet, has proven clinically useful in the treatment of chronic kidney disease patients with secondary hyperparathyroidism but is not widely used in earlier stages of renal disease due to the potential to predispose such patients to hypocalcaemia and hyperphosphatemia. The development of a biased CaSR ligand that is more selective for specific signaling pathway(s) leading only to beneficial effects may overcome this limitation. The detection of such stimulus-bias at a G protein-coupled receptor requires investigation across multiple signaling pathways and the development of methods to quantify the effects of allosteric ligands on orthosteric ligand affinity and cooperativity at each pathway. In the current study, we determined the effects of the calcimimetics, NPS-R568 or cinacalcet, and the calcilytic, NPS-2143, on Ca(o)(2+)-mediated intracellular Ca(2+) mobilization, ERK1/2 phosphorylation, and plasma membrane ruffling in a stably transfected human embryonic kidney 293-TREx c-myc-CaSR cell line and applied a novel analytical model to quantify these modulator effects. We present quantitative evidence for the generation of stimulus bias by both positive and negative allosteric modulators of the CaSR, manifested as greater allosteric modulation of intracellular Ca(2+) mobilization relative to ERK1/2 phosphorylation, and a higher affinity of the modulators for the state of the CaSR mediating plasma membrane ruffling relative to the other two pathways. Our findings provide the first evidence that an allosteric modulator used in clinical practice exhibits stimulus bias. 相似文献
74.
75.
Suzanne Gonzalez Chun Xu Mercedes Ramirez Juan Zavala Regina Armas Salvador A Contreras Javier Contreras Albana Dassori Robin J Leach Deborah Flores Alvaro Jerez Henriette Raventós Alfonso Ontiveros Humberto Nicolini Michael Escamilla 《Bipolar disorders》2013,15(2):206-214
Objectives: Through recent genome‐wide association studies (GWASs), several groups have reported significant association between variants in the calcium channel, voltage‐dependent, L‐type, alpha 1C subunit (CACNA1C) and bipolar disorder (BP) in European and European‐American cohorts. We performed a family‐based association study to determine whether CACNA1C is associated with BP in the Latino population. Methods: This study included 913 individuals from 215 Latino pedigrees recruited from the USA, Mexico, Guatemala, and Costa Rica. The Illumina GoldenGate Genotyping Assay was used to genotype 58 single‐nucleotide polymorphisms (SNPs) that spanned a 602.9‐kb region encompassing the CACNA1C gene including two SNPs (rs7297582 and rs1006737) previously shown to associate with BP. Individual SNP and haplotype association analyses were performed using Family‐Based Association Test (version 2.0.3) and Haploview (version 4.2) software. Results: An eight‐locus haplotype block that included these two markers showed significant association with BP (global marker permuted p = 0.0018) in the Latino population. For individual SNPs, this sample had insufficient power (10%) to detect associations with SNPs with minor effect (odds ratio = 1.15). Conclusions: Although we were not able to replicate findings of association between individual CACNA1C SNPs rs7297582 and rs1006737 and BP, we were able to replicate the GWAS signal reported for CACNA1C through a haplotype analysis that encompassed these previously reported significant SNPs. These results provide additional evidence that CACNA1C is associated with BP and provides the first evidence that variations in this gene might play a role in the pathogenesis of this disorder in the Latino population. 相似文献
76.
Antonia Wade Caroline Hayhurst Anthony Amato-Watkins Alistair Lammie Paul Leach 《Acta neurochirurgica》2013,155(8):1431-1435
Background
Pilocytic astrocytoma is one of the commonest subtypes of glioma to affect children. However, they are rarely diagnosed in patients over the age of 18 years. In adults, these tumours appear more frequently supra-tentorially than in the cerebellum and some reports suggest a different clinical course in adults. We reviewed ten patients aged 18 or over who had been operated on for cerebellar pilocytic astrocytoma to assess the impact of tumour biology and extent of resection on outcome in adults.Method
Patients were identified from a neuropathology database and a retrospective chart review of ten patients was performed. Recorded data included patient demographics, tumour location, presenting features, radiological appearance, extent of surgical resection, tumour recurrence and Ki-67 proliferation index.Results
Nine patients were men and one patient was a woman. Median follow up is 41.5 months (range 15–334 months). Complete surgical resection was achieved in nine of the patients operated in our institution. One patient had prior subtotal resection elsewhere. Tumour recurrence was seen only in the two patients with subtotal resection, at 7 and 25 years. Ki-67 ranged from <1 to 10 % and appears to have no correlation to recurrence. No patients in this series had adjuvant treatment.Conclusions
Cerebellar pilocytic astrocytomas in adults should be treated with macroscopic complete surgical resection whenever possible. If this is achieved, long-term survival rates are excellent, whereas subtotal resection carries a high risk of tumour recurrence. Ki-67 is less important prognostically than the extent of initial resection. 相似文献77.
Crohn's disease is an increasingly global health concern. Currently without a cure, it significantly alters the quality of life of Crohn's disease sufferers and places a heavy financial burden on the community. Recent reports show that the rising prevalence of Crohn's disease is no longer confined to Western countries, with considerable increases seen particularly in Asia. Nutritional problems are often associated with Crohn's disease, most notably in the paediatric population, with underweight and stunting commonly seen at presentation. In addition, linear growth retardation and pubertal delay can also manifest in these younger patients. Therefore, exclusive enteral nutrition has been used as a therapeutic option to treat Crohn's disease, in part to address the nutritional complications of the disease. Exclusive enteral nutrition can improve nutrition as well as induce remission at a rate equivalent to corticosteroids. It is safe particularly with long-term use and can induce mucosal healing, considered the gold standard for therapy, at a rate superior to corticosteroids. Exclusive enteral nutrition has thus become the preferred therapeutic option in many centres for the treatment of paediatric Crohn's disease. This review discusses the role of exclusive enteral nutrition as a therapeutic option for the treatment of Crohn's disease, as well as the latest findings into its mechanisms of action. 相似文献
78.
79.
Objective
This study aims to assess the efficacy and safety of vagal nerve stimulation (VNS) in children less than 12 years old operated on at the University Hospital Wales.Method
Retrospective review of patients undergoing VNS insertion, over a 3-year period, was undertaken. All children had a minimum follow-up period of 2 years. Sixteen patients were identified via the paediatric epilepsy surgery database. A case note review and telephone evaluation was conducted. Seizure frequency using the McHugh classification was the primary outcome measure, with anti-epileptic drug (AED) use as a secondary outcome measure.Results
There were 10 males and 6 females. The mean time with epilepsy prior to surgery was 5.7 years and the mean age at the time of surgery was 7.6 years. Overall, nine (56 %) children experienced a reduction in their seizure frequency of 50 % or more. Of these, four (25 %) had a reduction of more than 80 %. Seven children (44 %) had no reduction in their seizure frequency, although two of these patients reported benefit regarding seizure control and post-ictal recovery. The VNS system was removed in two patients due to infection and no benefit, respectively. Half of the cohort (50 %) reduced the number of anti-epileptic drugs post-surgery, and there was an overall mean reduction of AED of 0.5.Conclusion
This study suggests that VNS is a safe and effective adjuvant therapy in children under 12 years old, with over half reporting significant benefit. Further studies are needed to enable preoperative selection of patients in order to maximise the potential benefit. 相似文献80.
Erlick A.C. Pereira Aswin Chari Jonathan Hempenstall John C.D. Leach Hari Chandran Tom A.D. Cadoux-Hudson 《Journal of clinical neuroscience》2013,20(9):1250-1255
Anterior cervical discectomy and fusion (ACDF) is an established treatment for single-level cervical spondylotic myelopathy and radiculopathy, yet its stand-alone use for multi-level disease of the subaxial cervical spine remains controversial. We report a prospectively studied case series of 30 patients receiving polyetheretherketone (PEEK) cage fusion over three and four cervical levels without anterior plating. Seven (23.3%) four-level procedures (all C3 to C7) were performed, the other 23 (76.7%) being three-level, with 19 (64.4%) at C4 to C7 and four (12.3%) at C3 to C6. Long-term follow-up of more than 2 years was available in 67% of patients. This cohort showed statistically significant improvements in visual analogue score for neck pain (p = 0.0006), arm pain (p = 0.0003) and Japanese Orthopaedic Association myelopathy score (p = 0.002). Fused segment heights increased by 0.6–1.1%. Adjacent segment disease requiring ACDF at C3–4 was seen in 6.7% of patients (one after trauma) at a mean follow-up of 62 months. Same segment recurrence requiring posterior decompression with instrumented fusion was found in 10% of patients at a mean follow-up of 49 months, only one of whom had radiological evidence of cage subsidence. The results suggest the procedure is safe and effective with potentially less morbidity than anterior plating, shorter inpatient stays than posterior approaches, acceptable same segment recurrence and lower than predicted adjacent segment disease rates. 相似文献