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951.
Andrea Necchi Salvatore Lo Vullo Daniele Raggi Federica Perrone Patrizia Giannatempo Giuseppina Calareso Elena Togliardi Nicola Nicolai Luigi Piva Davide Biasoni Mario Catanzaro Tullio Torelli Silvia Stagni Maurizio Colecchia Adele Busico Marzia Pennati Nadia Zaffaroni Luigi Mariani Roberto Salvioni 《Urologic oncology》2018,36(1):8.e1-8.e8
Background
Outcomes of neoadjuvant chemotherapy in patients with muscle-invasive urothelial bladder carcinoma (MIUBC) should be improved. Sorafenib was combined with gemcitabine and cisplatin chemotherapy (SGC) in an open-label, single-arm, phase 2 trial (NCT01222676).Patients and methods
After transurethral resection of the bladder, T2–T4a N0 patients received four cycles of SGC followed by cystectomy. Sorafenib 400 mg q12h daily, continuously, was added to standard GC chemotherapy. In a Simon's 2-stage design, the primary endpoint was the pathologic complete response (pT0), assuming H0: ≤0.20 and H1: ≥0.40, with a type I and type II error of 5% and 10%, respectively.Results
From April 2011 to June 2016, 46 patients were enrolled. Pathologic T0 response was obtained in 20 patients (43.5%, 95% CI: 28.9–58.9); pT ≤ 1 in 25 (54.3%, 95% CI: 39.0–69.1). After a median follow-up of 35 months, the median progression-free survival was not reached (NR, interquartile range: 23.6–NR), nor was median overall survival (interquartile range: 30.3–NR). Hematologic and extrahematologic grade 3 to 4 adverse events occurred in 45.6% and 26.1% of patients, respectively. In 29 samples from responders (pT ≤ 1) and nonresponders, different distribution of missense mutations involved DNA-repair genes, RAS-RAF pathway genes, chromatin-remodeling genes, and HER-family genes. ERCC1 immunohistochemical expression was associated with pT ≤ 1 response (P = 0.047). The absence of a comparator arm prevented us to quantify sorafenib contribution.Conclusions
SGC combination was active in MIUBC, and the identified molecular features included alterations that may help personalize treatment in MIUBC with new more potent targeted agents, combined with chemotherapy. 相似文献952.
Kuo Chen-Yen Ku Cheng-Lung Lim Hye-Kyung Hsia Shao-Hsuan Lin Jainn-Jim Lo Chia-Chi Ding Jing-Ya Kuo Rei-Lin Casanova Jean-Laurent Zhang Shen-Ying Chang Luan-Yin Lin Tzou-Yien 《Journal of clinical immunology》2022,42(3):606-617
Journal of Clinical Immunology - Enterovirus A71 (EV71) causes a broad spectrum of childhood diseases, ranging from asymptomatic infection or self-limited hand-foot-and-mouth disease (HFMD) to... 相似文献
953.
Scudeller L Torti C Quiros-Roldan E Patroni A Lo Caputo S Moretti F Mazzotta F Donati E Vivarelli A Carosi G;GenPheRex Group of the MASTER Cohort 《The Journal of antimicrobial chemotherapy》2003,52(5):776-781
OBJECTIVES: The objective was to study genotypic correlates of discordant interpretations of amprenavir (APV) resistance between a rules-based algorithm and either recombinant phenotype or virtual phenotype. METHODS: HIV resistance mutations found in patients from the GenPheRex study were interpreted with VGI-TRUGENE (version 5.0; VGI) and compared with either recombinant-phenotype (Antivirogram, r-PHT) or virtual-phenotype (Virtual-Phenotype, v-PHT) interpreted through Virco biological cut-offs. RESULTS: Among 180 samples available, 56 (31.1%) were discordant with the observed genotype interpretation results, as a result of being judged as sensitive by r-PHT or v-PHT but resistant by VGI (S/R). Only the I84V mutation was almost invariably found in concordant resistant isolates compared with S/R isolates (60% versus 0%, respectively; P < 0.0001). Notwithstanding this, the number of multi-protease inhibitor-associated mutations (PAMs) was significantly higher in the concordant resistant isolates; the prevalence of >3 PAMs was 56.52% versus 33.93% in R/R and S/R isolates, respectively (P = 0.01). Correspondence analysis confirmed the relevance of PAMs, although additional mutations appeared to be correlated with APV resistance. CONCLUSIONS: The rate of discordance between rules-based and either r-PHT or v-PHT interpretations for APV was high. Mutation I84V and accumulation of >3 PAMs were found to be associated with resistance as interpreted with all systems tested. However, our results indicate that a number of mutations may have an impact on APV resistance, but that they are missed by current interpretation algorithms and this merits further investigations. 相似文献
954.
1 Versus 2-cm Excision Margins for pT2-pT4 Primary Cutaneous Melanoma (MelMarT): A Feasibility Study
Marc D. Moncrieff David Gyorki Robyn Saw Andrew J. Spillane Howard Peach Deemesh Oudit Jenny Geh Peter Dziewulski Ewan Wilson Paolo Matteucci Rowan Pritchard-Jones Roger Olofsson Bagge Frances C. Wright Nic Crampton Oliver Cassell Navid Jallali Adam Berger John Kelly Stephen Hamilton Amer Durrani Serigne Lo Elizabeth Paton Michael A. Henderson 《Annals of surgical oncology》2018,25(9):2541-2549
Background
There is a lack of consensus regarding optimal surgical excision margins for primary cutaneous melanoma?>?1 mm in Breslow thickness (BT). A narrower surgical margin is expected to be associated with lower morbidity, improved quality of life (QoL), and reduced cost. We report the results of a pilot international study (MelMarT) comparing a 1 versus 2-cm surgical margin for patients with primary melanoma?>?1 mm in BT.Methods
This phase III, multicentre trial [NCT02385214] administered by the Australia & New Zealand Medical Trials Group (ANZMTG 03.12) randomised patients with a primary cutaneous melanoma?>?1 mm in BT to a 1 versus 2-cm wide excision margin to be performed with sentinel lymph node biopsy. Surgical closure technique was at the discretion of the treating surgeon. Patients’ QoL was measured (FACT-M questionnaire) at baseline, 3, 6, and 12 months after randomisation.Results
Between January 2015 and June 2016, 400 patients were randomised from 17 centres in 5 countries. A total of 377 patients were available for analysis. Primary melanomas were located on the trunk (56.9%), extremities (35.6%), and head and neck (7.4%). More patients in the 2-cm margin group required reconstruction (34.9 vs. 13.6%; p?<?0.0001). There was an increased wound necrosis rate in the 2-cm arm (0.5 vs. 3.6%; p?=?0.036). After 12 months’ follow-up, no differences were noted in QoL between groups.Discussion
This pilot study demonstrates the feasibility of a large international RCT to provide a definitive answer to the optimal excision margin for patients with intermediate- to high-risk primary cutaneous melanoma.955.
956.
Tehrani F Rogers M Lo T Malinowski T Afuwape S Lum M Grundl B Terry M 《Journal of clinical monitoring and computing》2004,18(2):111-129
OBJECTIVE: Closed-loop mechanical ventilation has the potential to provide more effective ventilatory support to patients with less complexity than conventional ventilation. The purpose of this study was to investigate the effectiveness of an automatic technique for mechanical ventilation. METHODS: Two closed-loop control systems for mechanical ventilation are combined in this study. In one of the control systems several physiological data are used to automatically adjust the frequency and tidal volume of breaths of a patient. This method, which is patented under US Patent number 4986268, uses the criterion of minimal respiratory work rate to provide the patient with a natural pattern of breathing. The inputs to the system include data representing CO2 and O2 levels of the patient as well as respiratory compliance and airway resistance. The I:E ratio is adjusted on the basis of the respiratory time constant to allow for effective emptying of the lungs in expiration and to avoid intrinsic positive end expiratory pressure (PEEP). This system is combined with another closed-loop control system for automatic adjustment of the inspired fraction of oxygen of the patient. This controller uses the feedback of arterial oxygen saturation of the patient and combines a rapid stepwise control procedure with a proportional-integral-derivative (PID) control algorithm to automatically adjust the oxygen concentration in the patient's inspired gas. The dual closed-loop control system has been examined by using mechanical lung studies, computer simulations and animal experiments. RESULTS: In the mechanical lung studies, the ventilation controller adjusted the breathing frequency and tidal volume in a clinically appropriate manner in response to changes in respiratory mechanics. The results of computer simulations and animal studies under induced disturbances showed that blood gases were returned to the normal physiologic range in less than 25 s by the control system. In the animal experiments understeady-state conditions, the maximum standard deviations of arterial oxygen saturation and the end-tidal partial pressure of CO2 were +/- 1.76% and +/- 1.78 mmHg, respectively. CONCLUSION: The controller maintained the arterial blood gases within normal limits under steady-state conditions and the transient response of the system was robust under various disturbances. The results of the study have showed that the proposed dual closed-loop technique has effectively controlled mechanical ventilation under different test conditions. 相似文献
957.
Lo HJ Wang JS Lin CY Chen CG Hsiao TY Hsu CT Su CL Fann MJ Ching YT Yang YL 《Antimicrobial agents and chemotherapy》2005,49(3):1213-1215
The ERG3 gene in Candida albicans was identified as a gene whose mRNA level was higher in the cph1/cph1 efg1/efg1 double mutant than in the wild-type cells. Further study showed that Efg1, but not Cph1, negatively regulated ERG3. Mutations in EFG1 consistently increased the susceptibility of the cells to antifungal agents. 相似文献
958.
K B Neeves C T Lo C P Foley W M Saltzman W L Olbricht 《Journal of controlled release》2006,111(3):252-262
Convection enhanced drug delivery (CED) is a promising therapeutic method for treating diseases of the brain by enhancing the penetration of drugs. Most controlled release delivery methods rely on diffusion from a source to transport drugs throughout tissue. CED relies on direct infusion of drugs into tissue at a sufficiently high rate so that convective transport of drug is at least as important as diffusive transport. This work describes the fabrication and characterization of microfluidic probes for CED protocols and the role diffusion plays in determining penetration. Microfluidic channels were formed on silicon substrates by employing a sacrificial photoresist layer encased in a parylene structural layer. Flow in the microchannels was characterized by applying constant upstream pressures from 35 to 310 kPa, which resulted in flow rates of 0.5-4.5 microL/min. The devices were used to infuse Evans Blue and albumin in hydrogel brain phantoms. The results of these infusions were compared to a simple convection-diffusion model for infusions into porous media. In vivo infusions of albumin were performed in the gray matter of rats at upstream pressures of 35, 70, and 140 kPa. The microfabricated probes show reduced evidence of backflow along the device-tissue interface when compared with conventional needles used for CED. 相似文献
959.
The role of ERCP in choledocholithiasis 总被引:3,自引:0,他引:3
960.
Dobrez DG Lo Sasso AT Heinemann AW 《Archives of physical medicine and rehabilitation》2004,85(12):346-1914
OBJECTIVES: To estimate the difference between cost and prospective payment system (PPS) reimbursements for rehabilitation care and to simulate potential consequences of cost-reducing strategies. DESIGN: A retrospective study to estimate costs and functional status at discharge from care. SETTING: An academic, urban, rehabilitation hospital. PARTICIPANTS: Stroke patients on their first admission to a rehabilitation hospital between 1994 and 1998. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Cost was estimated from billing databases. Function was measured using the motor and cognitive components of the FIM instrument. RESULTS: PPS reimbursements were 10,825 dollars (37%) lower than costs. No matter how much therapy was reduced, the costs were still greater than the mean PPS reimbursement. A reduction in length of stay by 9.6 days was required to bring costs in line with the PPS reimbursement, reducing discharge cognitive function by 1.1 points (P <.01). Use of group therapy brought costs close to PPS reimbursement amount and improved discharge cognitive function by 0.5 points (P <.10). CONCLUSIONS: Our study shows the large difference between costs and expected PPS reimbursements that would have been observed before the PPS. Institutions have many options that reduce costs, with little effect on function at discharge. Future studies should determine the impact of evolving reimbursement rules on facilities financial status, and on patient outcomes. 相似文献