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1.
Mette Nissen Tiina‐Mari Ikheimo Jukka Huttunen Ville Leinonen Henna‐Kaisa Jyrkknen Mikael von und zu Fraunberg 《Neuromodulation》2021,24(1):102-111
ObjectiveSpinal cord stimulation (SCS) is an effective treatment in failed back surgery syndrome (FBSS). We studied the effect of preimplantation opioid use on SCS outcome and the effect of SCS on opioid use during a two-year follow-up period.Materials and methodsThe study cohort included 211 consecutive FBSS patients who underwent an SCS trial from January 1997 to March 2014. Participants were divided into groups, which were as follows: 1) SCS trial only (n = 47), 2) successful SCS (implanted and in use throughout the two-year follow-up period, n = 131), and 3) unsuccessful SCS (implanted but later explanted or revised due to inadequate pain relief, n = 29). Patients who underwent explantation for other reasons (n = 4) were excluded. Opioid purchase data from January 1995 to March 2016 were retrieved from national registries.ResultsHigher preimplantation opioid doses associated with unsuccessful SCS (ROC: AUC = 0.66, p = 0.009), with 35 morphine milligram equivalents (MME)/day as the optimal cutoff value. All opioids were discontinued in 23% of patients with successful SCS, but in none of the patients with unsuccessful SCS (p = 0.004). Strong opioids were discontinued in 39% of patients with successful SCS, but in none of the patients with unsuccessful SCS (p = 0.04). Mean opioid dose escalated from 18 ± 4 MME/day to 36 ± 6 MME/day with successful SCS and from 22 ± 8 MME/day to 82 ± 21 MME/day with unsuccessful SCS (p < 0.001).ConclusionsHigher preimplantation opioid doses were associated with SCS failure, suggesting the need for opioid tapering before implantation. With continuous SCS therapy and no explantation or revision due to inadequate pain relief, 39% of FBSS patients discontinued strong opioids, and 23% discontinued all opioids. This indicates that SCS should be considered before detrimental dose escalation. 相似文献
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Melanie A. Krook Julie W. Reeser Gabrielle Ernst Hannah Barker Max Wilberding Gary Li Hui-Zi Chen Sameek Roychowdhury 《British journal of cancer》2021,124(5):880
Fibroblast growth factor receptors (FGFRs) are aberrantly activated through single-nucleotide variants, gene fusions and copy number amplifications in 5–10% of all human cancers, although this frequency increases to 10–30% in urothelial carcinoma and intrahepatic cholangiocarcinoma. We begin this review by highlighting the diversity of FGFR genomic alterations identified in human cancers and the current challenges associated with the development of clinical-grade molecular diagnostic tests to accurately detect these alterations in the tissue and blood of patients. The past decade has seen significant advancements in the development of FGFR-targeted therapies, which include selective, non-selective and covalent small-molecule inhibitors, as well as monoclonal antibodies against the receptors. We describe the expanding landscape of anti-FGFR therapies that are being assessed in early phase and randomised controlled clinical trials, such as erdafitinib and pemigatinib, which are approved by the Food and Drug Administration for the treatment of FGFR3-mutated urothelial carcinoma and FGFR2-fusion cholangiocarcinoma, respectively. However, despite initial sensitivity to FGFR inhibition, acquired drug resistance leading to cancer progression develops in most patients. This phenomenon underscores the need to clearly delineate tumour-intrinsic and tumour-extrinsic mechanisms of resistance to facilitate the development of second-generation FGFR inhibitors and novel treatment strategies beyond progression on targeted therapy.Subject terms: Cancer, Cancer 相似文献
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Rene S. Hendriksen Pimlapas Leekitcharoenphon Matthew Mikoleit Jacob Dyring Jensen Rolf Sommer Kaas Louise Roer Heena B. Joshi Srirat Pornruangmong Chaiwat Pulsrikarn Gladys D. Gonzalez-Aviles E. Ascelijn Reuland Nashwan Al Naiemi Astrid Louise Wester Frank M. Aarestrup Henrik Hasman 《Journal of clinical microbiology》2015,53(2):677-680
One unreported case of extended-spectrum-beta-lactamase (ESBL)-producing Salmonella enterica serovar Typhi was identified, whole-genome sequence typed, among other analyses, and compared to other available genomes of S. Typhi. The reported strain was similar to a previously published strain harboring blaSHV-12 from the Philippines and likely part of an undetected outbreak, the first of ESBL-producing S. Typhi. 相似文献
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Clinical Epileptology - Der plötzliche unerwartete Tod stellt eine seltene, aber schwerwiegende Komplikation für Epilepsiepatienten dar. Das Risiko hierfür ist u. a. nachts und... 相似文献
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Peter Marhofer Malachy Columb Phil M. Hopkins Manfred Greher Daniela Marhofer Max R. Levi Bienzle Markus Zeitlinger 《British journal of anaesthesia》2019,122(4):525-531
Background
The efficacy of dexamethasone in extending the duration of local anaesthetic block is uncertain. In a randomised controlled triple blind crossover study in volunteers, we tested the hypothesis that neither i.v. nor perineurally administered dexamethasone prolongs the sensory block achieved with ropivacaine.Methods
Ultrasound-guided ulnar nerve blocks (ropivacaine 0.75% wt/vol, 3 ml, with saline 1 ml with or without dexamethasone 4 mg) were performed on three occasions in 24 male volunteers along with an i.v. injection of saline 1 ml with or without dexamethasone 4 mg. The combinations of saline and dexamethasone were as follows: control group, perineural and i.v. saline; perineural group, perineural dexamethasone and i.v. saline; i.v. group, perineural saline and i.v. dexamethasone. Sensory block was measured using a VAS in response to pinprick testing. The duration of sensory block was the primary outcome and time to onset of sensory block the secondary outcome.Results
All 24 subjects completed the trial. The median [inter-quartile range (IQR)] duration of sensory block was 6.87 (5.85–7.62) h in the control group, 7.37 (5.78–7.93) h in the perineural group and 7.37 (6.10–7.97) h in the i.v. group (P=0.61). There was also no significant difference in block onset time between the three groups.Conclusion
Dexamethasone 4 mg has no clinically relevant effect on the duration of sensory block provided by ropivacaine applied to the ulnar nerve.Clinical trial registration
DRKS, 00014604; EudraCT, 2018-001221-98. 相似文献10.