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91.
Prado-Prado F García-Mera X Abeijón P Alonso N Caamaño O Yáñez M Gárate T Mezo M González-Warleta M Muiño L Ubeira FM González-Díaz H 《European journal of medicinal chemistry》2011,46(4):1074-1094
There are many drugs described with very different affinity to a large number of receptors. In this work, we selected Drug-Target pairs (DTPs/nDTPs) of drugs with high affinity/non-affinity for different targets like proteins. Quantitative Structure-Activity Relationships (QSAR) models become a very useful tool in this context to substantially reduce time and resources consuming experiments. Unfortunately, most QSAR models predict activity against only one protein. To solve this problem, we developed here a multi-target QSAR (mt-QSAR) classifier using the MARCH-INSIDE technique to calculate structural parameters of drug and target plus one Artificial Neuronal Network (ANN) to seek the model. The best ANN model found is a Multi-Layer Perceptron (MLP) with profile MLP 32:32-15-1:1. This MLP classifies correctly 623 out of 678 DTPs (Sensitivity = 91.89%) and 2995 out of 3234 nDTPs (Specificity = 92.61%), corresponding to training Accuracy = 92.48%. The validation of the model was carried out by means of external predicting series. The model classifies correctly 313 out of 338 DTPs (Sensitivity = 92.60%) and 1411 out of 1534 nDTP (Specificity = 91.98%) in validation series, corresponding to total Accuracy = 92.09% for validation series (Predictability). This model favorably compares with other LDA and ANN models developed in this work and Machine Learning classifiers published before to address the same problem in different aspects. These mt-QSARs offer also a good opportunity to construct drug-protein Complex Networks (CNs) that can be used to explore large and complex drug-protein receptors databases. Finally, we illustrated two practical uses of this model with two different experiments. In experiment 1, we report prediction, synthesis, characterization, and MAO-A and MAO-B pharmacological assay of 10 rasagiline derivatives promising for anti-Parkinson drug design. In experiment 2, we report sampling, parasite culture, SEC and 1DE sample preparation, MALDI-TOF MS and MS/MS analysis, MASCOT search, MM/MD 3D structure modeling, and QSAR prediction for different peptides of hemoglobin found in the proteome of the human parasite Fasciola hepatica; which is promising for anti-parasite drug targets discovery. 相似文献
92.
Orcajo B Muruzabal F Isasmendi MC Gutierrez N Sánchez M Orive G Anitua E 《Diabetes research and clinical practice》2011,93(2):e65-e67
A 71 year old person with diabetes with a severe mal perforant ulcer in the right foot was treated twice with autologous plasma-rich in growth factors (PRGF) obtained from her own blood. After PRGF treatment the severe mal perforant ulcer completely healed in 10 weeks. 相似文献
93.
Lithium‐ion batteries are part of modern life, being present in daily‐used objects such as mobile phones, tablets, computers, watches, sport accessories, electric scooters, and cars. The next‐generation batteries require the development of innovative polymers that help to improve their performance in terms of power density, cyclability, raw materials' availability, low weight, printability, flexibility, sustainability, or security. This article highlights recent developments in the area of redox‐active, electronic/ionic conducting polymers. This includes the development of innovative binders for electrodes, polymer electrolytes, and redox polymers. All these new polymer developments are leading to new battery technologies such as metal–polymer batteries, organic batteries, polymer–air, and redox–flow batteries, which are expected to complement the current lithium‐ion technologies in the future. 相似文献
94.
Eva Barragán María Carmen Chillón Remedios Castelló-Cros Nerea Marcotegui María Isabel Prieto Montserrat Hoyos Raffaella Pippa Marta Llop Amaia Etxabe José Cervera Gabriela Rodríguez Ismael Bu?o José Rifón Jorge Sierra Marcos González María J. Calasanz Miguel A. Sanz María D. Odero 《Haematologica》2015,100(5):e183-e185
95.
José M. Quintana Ane Antón-Ladisla Nerea González Santiago Lázaro Marisa Baré Nerea Fernández de Larrea Maximino Redondo Eduardo Briones Antonio Escobar Cristina Sarasqueta Susana García-Gutierrez 《European journal of surgical oncology》2018,44(9):1344-1353
Objective
There is limited information on health service use or patient-reported outcomes when comparing the effectiveness of laparoscopic with that of open surgery. The aim was to compare the effectiveness of laparoscopic with that of open surgery up to 2 years after intervention in patients with colon cancer.Methods
Prospective cohort study of patients with colon cancer who underwent surgery (laparoscopic or open surgery) between June 2010 and December 2012, at 22 hospitals. Main outcomes of the study were mortality, complications, reoperation, readmission, and patient-reported outcome measures (PROMs), as measured using the Hospital Anxiety and Depression Scale, Duke-UNC, EuroQol-5D, and European Organisation for Research and Treatment of Cancer-Q30 and Q29 at baseline, and 30 days and 1 and 2 years after surgery. Multivariable multilevel logistic regression and generalized linear models were used in analyses after adjusting for specific propensity scores developed for each outcome and time point.Results
In the multivariable analysis, the complication rates up to 30 days (infectious, surgical, and medical) and 1 year (surgical), and readmission rate at 30 days and at 2 years were higher among patients who underwent open surgery than among those who underwent laparoscopic surgery. There were no differences between the two surgical approaches in all other parameters assessed and in changes of all PROMs.Conclusions
Though in most outcomes both surgical approaches provide similar results up to 2 years after intervention, still the rates of some complications and readmission, mainly up to 30 days, are higher in open surgery.96.
Khan AE Gallo V Linseisen J Kaaks R Rohrmann S Raaschou-Nielsen O Tjønneland A Johnsen HE Overvad K Bergmann MM Boeing H Benetou V Psaltopoulou T Trichopoulou A Masala G Mattiello A Grioni S Tumino R Vermeulen RC Peeters PH Bueno-de-Mesquita HB Ros MM Lund E Ardanaz E Chirlaque MD Jakszyn P Larrañaga N Losada A Becker N Nieters A Martínez-García C Agren A Hallmans G Berglund G Manjer J Allen NE Key TJ Bingham S Khaw KT Slimani N Ferrari P Boffetta P Norat T Vineis P Riboli E;EPIC Group 《Haematologica》2008,93(6):842-850
97.
98.
Raquel de la Varga‐Martínez Beatriz Rodríguez‐Bayona Antonio Campos‐Caro Gustavo A Aez Fermín Medina‐Varo Carmen Rodríguez 《European journal of immunology》2019,49(7):1107-1116
Systemic lupus erythematosus and rheumatoid arthritis are autoimmune diseases characterised by B‐cell hyperactivation and production of autoantibodies (AutoAbs) against various self‐antigens, including extractable nuclear antigens and citrullinated peptides. Therefore, B lymphocytes and antibody‐secreting cells are considered relevant targets for therapies. However, isolation and characterisation of auto‐reactive specific B lymphocytes are limited, primarily due to technical issues. In this work, we purified extractable nuclear antigen‐specific and citrullinated peptide‐specific auto‐reactive B lymphocytes by magnetic selection with ENA‐ and citrullinated peptide‐bound immunobeads. We obtained blood auto‐reactive B lymphocytes from most patients. Their nature was primarily naïve B cells, some of them in an active status, with low levels of somatic hypermutations in the immunoglobulin heavy‐chain variable regions. Their presence correlated with serum levels of autoAb. Auto‐reactive B lymphocytes were able to differentiate into auto‐reactive antibody‐secreting cells under conditions of stimulation. In addition, based on the presence of circulating auto‐reactive B cells and/or antibody‐secreting cells, four different profiles were described in lupus patients. Thus, tracking auto‐reactive B cells and/or antibody‐secreting cells in patient blood could represent a biomarker for deciding whether to use therapies blocking either B cells, plasma cells or both, as well as a new tool for monitoring minimal residual autoimmune disease in patients. 相似文献
99.
Terry G. J. Derks David F. Rodriguez-Buritica Ayesha Ahmad Foekje de Boer María L. Couce Sarah C. Grünert Philippe Labrune Nerea Lpez Maldonado Carolina Fischinger Moura de Souza Rebecca Riba-Wolman Alessandro Rossi Heather Saavedra Rupal Naik Gupta Vassili Valayannopoulos John Mitchell 《Nutrients》2021,13(11)
Glycogen storage disease type Ia (GSDIa) is caused by defective glucose-6-phosphatase, a key enzyme in carbohydrate metabolism. Affected individuals cannot release glucose during fasting and accumulate excess glycogen and fat in the liver and kidney, putting them at risk of severe hypoglycaemia and secondary metabolic perturbations. Good glycaemic/metabolic control through strict dietary treatment and regular doses of uncooked cornstarch (UCCS) is essential for preventing hypoglycaemia and long-term complications. Dietary treatment has improved the prognosis for patients with GSDIa; however, the disease itself, its management and monitoring have significant physical, psychological and psychosocial burden on individuals and parents/caregivers. Hypoglycaemia risk persists if a single dose of UCCS is delayed/missed or in cases of gastrointestinal intolerance. UCCS therapy is imprecise, does not treat the cause of disease, may trigger secondary metabolic manifestations and may not prevent long-term complications. We review the importance of and challenges associated with achieving good glycaemic/metabolic control in individuals with GSDIa and how this should be balanced with age-specific psychosocial development towards independence, management of anxiety and preservation of quality of life (QoL). The unmet need for treatment strategies that address the cause of disease, restore glucose homeostasis, reduce the risk of hypoglycaemia/secondary metabolic perturbations and improve QoL is also discussed. 相似文献
100.