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61.
Defining outcomes for β‐cell replacement therapy in the treatment of diabetes: a consensus report on the Igls criteria from the IPITA/EPITA opinion leaders workshop
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Michael R. Rickels Peter G. Stock Eelco J. P. de Koning Lorenzo Piemonti Johann Pratschke Rodolfo Alejandro Melena D. Bellin Thierry Berney Pratik Choudhary Paul R. Johnson Raja Kandaswamy Thomas W. H. Kay Bart Keymeulen Yogish C. Kudva Esther Latres Robert M. Langer Roger Lehmann Barbara Ludwig James F. Markmann Marjana Marinac Jon S. Odorico François Pattou Peter A. Senior James A. M. Shaw Marie‐Christine Vantyghem Steven White 《Transplant international》2018,31(4):343-352
β‐cell replacement therapy, available currently as pancreas or islet transplantation, has developed without a clear definition of graft functional and clinical outcomes. The International Pancreas & Islet Transplant Association (IPITA) and European Pancreas & Islet Transplantation Association (EPITA) held a workshop to develop consensus for an IPITA/EPITA Statement on the definition of function and failure of current and future forms of β‐cell replacement therapy. There was consensus that β‐cell replacement therapy could be considered as a treatment for β‐cell failure, regardless of etiology and without requiring undetectable C‐peptide, accompanied by glycemic instability with either problematic hypoglycemia or hyperglycemia. Glycemic control should be assessed at a minimum by glycated hemoglobin (HbA1c) and the occurrence of severe hypoglycemia. Optimal β‐cell graft function is defined by near‐normal glycemic control [HbA1c ≤ 6.5% (48 mmol/mol)] without severe hypoglycemia or requirement for insulin or other antihyperglycemic therapy, and with an increase over pretransplant measurement of C‐peptide. Good β‐cell graft function requires HbA1c < 7.0% (53 mmol/mol) without severe hypoglycemia and with a significant (>50%) reduction in insulin requirements and restoration of clinically significant C‐peptide production. Marginal β‐cell graft function is defined by failure to achieve HbA1c < 7.0% (53 mmol/mol), the occurrence of any severe hypoglycemia, or less than 50% reduction in insulin requirements when there is restoration of clinically significant C‐peptide production documented by improvement in hypoglycemia awareness/severity, or glycemic variability/lability. A failed β‐cell graft is defined by the absence of any evidence for clinically significant C‐peptide production. Optimal and good functional outcomes are considered successful clinical outcomes. 相似文献
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Quantitative diffusion tensor MRI fiber tractography of sensorimotor white matter development in premature infants 总被引:8,自引:0,他引:8
Berman JI Mukherjee P Partridge SC Miller SP Ferriero DM Barkovich AJ Vigneron DB Henry RG 《NeuroImage》2005,27(4):8-871
Diffusion tensor MRI (DTI) fiber tracking is the first non-invasive and in vivo technique for the delineation and quantitation of specific white matter pathways. In this study, quantitative fiber tracking was used to assess the structural development of the motor tract and somatosensory radiation in premature human newborns. These pathways are unmyelinated in the youngest premature infants and begin to myelinate during late preterm maturation. Previous studies have only been able to delineate parts of these pathways that could be manually outlined in 2D based on anatomical landmarks. Furthermore, these previous studies could not separate motor and sensory regions. A high-sensitivity neonatal head coil was employed in conjunction with an MR-compatible incubator to perform high-resolution imaging of the premature infant brain. The motor and somatosensory tracts were successfully delineated with 3D DTI fiber tracking in 37 exams of preterm newborns between 28 and 43 weeks gestational age. Both streamline deterministic and probabilistic methods were employed to perform quantitative fiber tractography. Tract-specific measurements of diffusion parameters including fractional anisotropy, directionally averaged diffusivity, and eigenvalues were obtained from the motor and sensory pathways. Using both deterministic and probabilistic fiber tracking, all tract-specific diffusion parameters were found to be significantly correlated with age and the motor tracts were found to have higher anisotropy and lower diffusivity than the sensory pathway. By segmenting the 3D fiber tracks by slice, measurements from different axial levels of the brain were found to vary with region and age. In summary, deterministic and probabilistic DTI fiber tracking methods were used to quantify the developmental changes of motor and somatosensory pathways in premature infants. 相似文献
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Ely EW Girard TD Shintani AK Jackson JC Gordon SM Thomason JW Pun BT Canonico AE Light RW Pandharipande P Laskowitz DT 《Critical care medicine》2007,35(1):112-117
OBJECTIVE: To test for an association between apolipoprotein E (APOE) genotypes and duration of intensive care unit delirium. DESIGN: Prospective, observational cohort study. SETTING: A 541-bed, community-based teaching hospital. PATIENTS: Fifty-three mechanically ventilated intensive care unit patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients were managed with standardized sedation and ventilator weaning protocols as part of an ongoing clinical trial and were evaluated prospectively for delirium with the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). DNA was extracted from whole blood samples obtained on enrollment, and APOE genotype was determined using polymerase chain reaction followed by restriction enzyme digestion by investigators blinded to the clinical information. Delirium occurred in 47 (89%) patients at some point during the intensive care unit stay. Of the 53 patients, 12 (23%) had an APOE4 allele (APOE4+) and 41 (77%) had only APOE2 or APOE3 alleles (APOE4-). APOE4+ patients were younger (53.2 +/- 21.9 vs. 65.4 +/- 13.4, p = .08) and less often admitted for pneumonia (0% vs. 29.3%, p = .05) compared with APOE4- patients, yet they had a duration of delirium that was twice as long: median (interquartile range), 4 (3, 4.5) vs. 2 (1, 4) days (p = .05). No other clinical outcomes were significantly different between the APOE4+ and APOE4- patients. Using multivariable regression analysis to adjust for age, admission diagnosis of sepsis or acute respiratory distress syndrome or pneumonia, severity of illness, and duration of coma, the presence of APOE4 allele was the strongest predictor of delirium duration (odds ratio, 7.32; 95% confidence interval, 1.82-29.51, p = .005). CONCLUSIONS: APOE4 allele represents the first demonstrated genetic predisposition to longer duration of delirium in humans. 相似文献
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Irappa Madabhavi Apurva Patel Asha Anand Pritam Kataria Nagaveni Kadakol Malay Sarkar 《Journal of the Association for Vascular Access》2018,23(1):23-29
Background
Effective and reliable venous access is among the cornerstones of modern medical therapy in oncology.Materials and Methods
This was a prospective observational study of collected data of patients with a diagnosis of any cancer, at a tertiary care oncology hospital in Ahmadabad, Gujarat, India, during a 2-year period.Results
A Hickman catheter was inserted in 200 patients and most commonly used in solid malignancies (n?=?103; 51.5%), followed by hematologic conditions (n?=?93; 48.5%). Among solid malignancies, hepatoblastoma (n?=?21; 10.5%) was the most common indication, whereas in hematologic malignancies acute lymphoblastic leukemia was the most common indication (n?=?56; 28%) for Hickman catheter insertion. Hickman catheters were inserted most commonly in the right side (n?=?170; 85%) of the venous system. The various complications in the Hickman study group in descending order were 28 patients (14%) developed arrhythmias, 15 patients (7.5%) developed infection, 12 patients (6%) developed bleeding, 8 patients (4%) developed pneumothorax, 7 patients (3.5%) developed catheter blockage, and 6 patients (3%) required premature catheter removal. The median time of Hickman catheter in situ was 207 days.Conclusions
The most disturbing aspect of treatment of patients with cancer is multiple painful venipunctures made for administration of cytotoxic agents, antibiotics, blood products, and nutritional supplements. The focus of this prospective observational research was to study the various indications for Hickman catheter in different solid and hematologic malignancies as well as the various complications and outcomes in pediatric and adult cancer patients. 相似文献67.
The combination of mapping functional cortical neurons by intraoperative cortical stimulation and axonal architecture by diffusion tensor MRI fiber tracking can be used to delineate the pathways between functional regions. In this study the authors investigated the feasibility of combining these techniques to yield connectivity associated with motor speech and naming. Diffusion tensor MRI fiber tracking provides maps of axonal bundles and was combined with intraoperative mapping of eloquent cortex for a patient undergoing brain tumor surgery. Tracks from eight stimulated sites in the inferior frontal cortex including mouth motor, speech arrest, and anomia were generated from the diffusion tensor MRI data. The regions connected by the fiber tracking were compared to foci from previous functional imaging reports on language tasks. Connections were found between speech arrest, mouth motor, and anomia sites and the SMA proper and cerebral peduncle. The speech arrest and a mouth motor site were also seen to connect to the putamen via the external capsule. This is the first demonstration of delineation of subcortical pathways using diffusion tensor MRI fiber tracking with intraoperative cortical stimulation. The combined techniques may provide improved preservation of eloquent regions during neurological surgery, and may provide access to direct connectivity information between functional regions of the brain. 相似文献
68.
Jatin Machhi Anshuman Sinha Pratik Patel Ashish M. Kanhed Pragnesh Upadhyay Ashutosh Tripathi Zalak S. Parikh Ragitha Chruvattil Prakash P. Pillai Sarita Gupta Kirti Patel Rajani Giridhar Mange Ram Yadav 《Neurotoxicity research》2016,29(4):495-513
Previous reports suggest that Alzheimer’s disease is protected by cholinesterase inhibitors. We synthesized some isoalloxazine derivatives and evaluated them using in vitro cholinesterase inhibition assay. Two of the compounds (7m and 7q) were figured out as potent cholinesterase inhibitors. They further showed anti-Aβ aggregatory activity in the in vitro assay. The current study deals with the evaluation of neuroprotective potentials of the potent compounds (7m and 7q) using different in vitro and in vivo experiments. The compounds were first assessed for their tendency to cross blood–brain barrier using in vitro permeation assay. They were evaluated using scopolamine-induced amnesic mice model. Additionally, ROS scavenging and anti-apoptotic properties of 7m and 7q were established against Aβ1–42-induced toxicity in rat hippocampal neuronal cells. 7m and 7q were also evaluated using Aβ1–42-induced Alzheimer’s rat model. Lastly, their involvement in Wnt/β-catenin pathway was also demonstrated. The results indicated good CNS penetration for 7m and 7q. The neuroprotective effects of 7m and 7q were evidenced by improved cognitive ability in both scopolamine and Aβ1–42-induced Alzheimer’s-like condition in rodents. The in vivo results also confirmed their anti-cholinesterase and anti-oxidant potential. Immunoblot results showed that treatment with 7m and 7q decreased Aβ1–42, p-tau, cleaved caspase-3, and cleaved PARP levels in Aβ1–42-induced Alzheimer’s rat brain. Additionally, immunoblot results demonstrated that 7m and 7q activated the Wnt/β-catenin pathway as evidenced by increased p-GSK-3, β-catenin, and neuroD1 levels in Aβ1–42-induced Alzheimer’s rat brain. These findings have shown that isoalloxazine derivatives (7m and 7q) could be the potential leads for developing effective drugs for the treatment of AD. 相似文献
69.
Reciprocal white matter alterations due to 16p11.2 chromosomal deletions versus duplications
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Nicholas J. Pojman Tony Thieu Polina Bukshpun Mari L.J. Wakahiro Elysa J. Marco Jeffrey I. Berman John E. Spiro Wendy K. Chung Randy L. Buckner Timothy P.L. Roberts Srikantan S. Nagarajan Elliott H. Sherr Pratik Mukherjee 《Human brain mapping》2016,37(8):2833-2848
Copy number variants at the 16p11.2 chromosomal locus are associated with several neuropsychiatric disorders, including autism, schizophrenia, bipolar disorder, attention‐deficit hyperactivity disorder, and speech and language disorders. A gene dosage dependence has been suggested, with 16p11.2 deletion carriers demonstrating higher body mass index and head circumference, and 16p11.2 duplication carriers demonstrating lower body mass index and head circumference. Here, we use diffusion tensor imaging to elucidate this reciprocal relationship in white matter organization, showing widespread increases of fractional anisotropy throughout the supratentorial white matter in pediatric deletion carriers and, in contrast, extensive decreases of white matter fractional anisotropy in pediatric and adult duplication carriers. We find associations of these white matter alterations with cognitive and behavioral impairments. We further demonstrate the value of imaging metrics for characterizing the copy number variant phenotype by employing linear discriminant analysis to predict the gene dosage status of the study subjects. These results show an effect of 16p11.2 gene dosage on white matter microstructure, and further suggest that opposite changes in diffusion tensor imaging metrics can lead to similar cognitive and behavioral deficits. Given the large effect sizes found in this study, our results support the view that specific genetic variations are more strongly associated with specific brain alterations than are shared neuropsychiatric diagnoses. Hum Brain Mapp 37:2833–2848, 2016. © 2016 Wiley Periodicals, Inc. 相似文献
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