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Response rate,durability of response,and survival after thalidomide therapy for relapsed multiple myeloma 总被引:12,自引:0,他引:12
Kumar S Gertz MA Dispenzieri A Lacy MQ Geyer SM Iturria NL Fonseca R Hayman SR Lust JA Kyle RA Greipp PR Witzig TE Rajkumar SV 《Mayo Clinic proceedings. Mayo Clinic》2003,78(1):34-39
OBJECTIVE: To assess response rate, duration of response, progression-free survival, and toxicity of thalidomide in patients with relapsed multiple myeloma. PATIENTS AND METHODS: Thirty-two patients with relapsed multiple myeloma were entered into the study between April 29, 1999, and June 20, 2000. They were given oral thalidomide at a dosage of 200 mg/d for 2 weeks, which was then increased as tolerated to a maximum of 800 mg/d. The primary end point of the study was response rate. RESULTS: The median age of the patients was 67 years (range, 36-78 years). Prior chemotherapy had failed in all patients, and stem cell transplantation had failed in 5 patients (16%). There were 10 confirmed responses, yielding a response rate of 31%. In addition, there was 1 unconfirmed partial response and 7 minimal responses with no complete responses. The median duration of response was 11.9 months (range, 3.7-203 months). Overall, 20 patients have died, and 26 patients have experienced disease progression. The median follow-up of surviving patients was 28.5 months (range, 193-34.0 months), with a median progression-free survival of 8.6 months (95% confidence interval [CI], 4.7-16 months). The median progression-free survival among the responding patients was 15.7 months (95% CI, 8.6-25.6 months). The median overall survival for the entire group was 22 months (95% CI, 10.6-35.9 months). The most common treatment-related nonhematologic toxic effects (grade >3) were neuropathy (16%), sedation (13%), febrile neutropenia (6%), and constipation (6%). CONCLUSIONS: Thalidomide is useful in the treatment of patients with relapsed multiple myeloma and produced durable response in approximately one third of patients, with median response duration of nearly 1 year. 相似文献
23.
Soujanya Bogarapu Michael D. Puchalski Melanie D. Everitt Richard V. Williams Hsin-Yi Weng Shaji C. Menon 《Pediatric cardiology》2016,37(4):663-673
Myocardial fibrosis is a risk factor for sudden cardiac death in hypertrophic cardiomyopathy (HCM) and is conventionally identified by cardiac magnetic resonance imaging (CMR) using late gadolinium enhancement (LGE). This study evaluates utility of a novel 16-segment CMR feature tracking (CMR-FT) technique for measuring left ventricular (LV) strain (S) and strain rate (SR) on non-contrast cine images to detect myocardial fibrosis in pediatric HCM. We hypothesized that CMR-FT-derived S and SR will accurately differentiate HCM patients with and without myocardial fibrosis. Consecutive children with HCM who underwent CMR with LGE at our institution from 2006 to 2014 were included. Global and regional longitudinal, radial and circumferential S and SR of the LV in 2D and 3D were obtained using a CMR-FT software. Comparisons were made between HCM patients with (+LGE) and without (?LGE) delayed enhancement. Of the 29 HCM patients (mean age 13.5 ± 6.1 years; 52 % males), 11 (40 %) patients (mean age 17.5 ± 8.4 years) had +LGE. Global longitudinal, circumferential and radial S and SR were lower in +LGE compared to ?LGE patients, in both 2D and 3D. Regional analysis revealed lower segmental S and SR in the septum with fibrosis compared to free wall without fibrosis. A global longitudinal S of ≤ ?12.8 had 91 % sensitivity and 89 % specificity for detection of LGE. In pediatric HCM patients with myocardial fibrosis, global LV longitudinal, circumferential and radial S and SR were reduced, specifically in areas of fibrosis. A global longitudinal S of ≤ ?12.8 detected patients with fibrosis with high degree of accuracy. This novel CMR-FT technique may be useful to identify myocardial fibrosis and risk-stratify pediatric HCM without use of contrast agents. 相似文献
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Acquired von Willebrand's disease or syndrome (AVWS) is a rare bleeding disorder distinguished from congenital von Willebrand's disease by age at presentation and absence of personal and family history of bleeding disorders. We report on 22 patients with AVWS seen over 25 years. Mean age at diagnosis was 61.3 years (range 38-86 years); most patients had a spontaneous or a post-operative hemorrhage at presentation. Gastrointestinal bleeding and epistaxis were the most common spontaneous symptoms. Bleeding time was prolonged in most patients, associated with marked reductions in plasma von Willebrand factor antigen and ristocetin cofactor activity. Plasma VWF multimer distribution was normal (type 1 pattern) in 5 patients, indeterminate (no multimers detectable) in 6 patients (type 3 pattern), and abnormal (decreased higher-molecular-weight multimers, type 2 pattern) in 11 patients. None of 17 patients tested had an inhibitor of ristocetin cofactor activity. An underlying malignant or benign hematologic disease was found in 18 patients, and 1 patient had Crohn's disease. Desmopressin was effective in only half the patients so treated, but all patients responded to treatment with VWF-containing concentrates. Resolution of AVWS occurred with therapy of lymphoma (1 patient) and chronic lymphocytic leukemia (1 patient). Sixteen patients were alive at last follow-up; no deaths were related to bleeding. AVWS may be more prevalent than has been appreciated; we estimate up to 0.04%. Awareness of the existence of AVWS is essential for diagnosis and appropriate management. Therapy of associated diseases may improve the bleeding disorder. 相似文献
26.
Efstathios Kastritis Ashutosh Wechalekar Stefan Schönland Vaishali Sanchorawala Giampaolo Merlini Giovanni Palladini Monique Minnema Murielle Roussel Arnaud Jaccard Ute Hegenbart Shaji Kumar Maria T. Cibeira Joan Blade Meletios A. Dimopoulos 《British journal of haematology》2020,190(3):346-357
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated coronavirus disease 2019 (COVID-19) is primarily manifested as a respiratory tract infection, but may affect and cause complications in multiple organ systems (cardiovascular, gastrointestinal, kidneys, haematopoietic and immune systems), while no proven specific therapy exists. The challenges associated with COVID-19 are even greater for patients with light chain (AL) amyloidosis, a rare multisystemic disease affecting the heart, kidneys, liver, gastrointestinal and nervous system. Patients with AL amyloidosis may need to receive chemotherapy, which probably increases infection risk. Management of COVID-19 may be particularly challenging in patients with AL amyloidosis, who often present with cardiac dysfunction, nephrotic syndrome, neuropathy, low blood pressure and gastrointestinal symptoms. In addition, patients with AL amyloidosis may be more susceptible to toxicities of drugs used to manage COVID-19. Access to health care may be difficult or limited, diagnosis of AL amyloidosis may be delayed with detrimental consequences and treatment administration may need modification. Both patients and treating physicians need to adapt in a new reality. 相似文献
27.
Eli Muchtar Morie A. Gertz Martha Q. Lacy Nelson Leung Francis K. Buadi David Dingli Suzanne R. Hayman Ronald S. Go Prashant Kapoor Wilson Gonsalves Taxiarchis V. Kourelis Rahma Warsame Yi Lisa Hwa Amie Fonder Miriam Hobbs Stephen Russell John A. Lust Mustaqeem Siddiqui S. Vincent Rajkumar Robert A. Kyle Shaji K. Kumar Angela Dispenzieri 《American journal of hematology》2020,95(11):1280-1287
Response assessment in light chain (AL) amyloidosis is based on serum and urine monoclonal protein studies. Newly diagnosed patients (n = 373) who achieved very good partial response or complete response (CR) to first line therapy were assessed for the survival impact of each of the monoclonal protein studies. At end of therapy (EOT), negative serum/urine immunofixation (IFE) was achieved in 61% of patients, 72% achieved normal serum free light chain ratio (sFLCR), and the median involved free light chain (iFLC) and difference between involved to uninvolved light chain (dFLC) were 17 mg/L and 5 mg/L, respectively. Overall, 46% of patients achieved a CR at EOT. At EOT, iFLC ≤20 mg/L and dFLC ≤10 mg/L were additive in survival discrimination to negative serum/urine IFE and were independent predictors of overall survival. In contrast, normalization of sFLCR did not add survival discrimination to serum/urine IFE and was not independent predictor of survival. We propose a new definition for hematological CR to include serum/urine IFE negativity plus iFLC ≤20 mg/L or dFLC ≤10 mg/L, instead of the current definition of serum/urine IFE negativity and normal sFLCR. Complete response using dFLC ≤10 mg/L had the best performance in those with significant renal dysfunction and by light chain isotype, making it the preferred partner to IFE. Validation of these results in a multicenter cohort is warranted. 相似文献
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Nelson Leung Siobhan V. Glavey Shaji Kumar Angela Dispenzieri Francis K. Buadi David Dingli Martha Q. Lacy Suzanne R. Hayman John A. Lust Stephen J. Russell Steven R. Zeldenrust S. Vincent Rajkumar Morie A. Gertz 《Haematologica》2013,98(6):988-992
Organ response correlates with overall survival in patients with immunoglobulin light chain amyloidosis and is the goal of treatment. This study evaluates the current renal response criteria and their ability to predict overall survival. Patients with immunoglobulin light chain amyloidosis who underwent autologous stem cell transplantation between 1995 and 2010 were recruited. Eligibility criteria included >1 g/dL of proteinuria, dialysis independence at baseline and within the first year of autologous stem cell transplantation, and a minimum follow-up of 1 year. Responses were assessed by the best values after autologous stem cell transplantation. The difference between involved and uninvolved serum free light chain levels was used to determine hematologic response. Increases in serum creatinine were calculated from the highest creatinine after autologous stem cell transplantation. Inclusion and exclusion criteria were met by 141 patients. These patients had a median follow-up of 52 months. Superior overall survival was observed in patients with a >75% reduction in proteinuria and those who had a >95% reduction had additional benefits. The overall survival of patients with >50% to ≤75% proteinuria was similar to that of patients with ≤50% reduction. A rise in serum creatinine >25% was not associated with a poorer outcome in patients with a >75% reduction in proteinuria. Deeper hematologic responses were associated with higher rates of proteinuria reduction. These results suggest that further evaluation of the current renal response criteria is needed. In particular, discrimination of the renal response into complete and partial categories and modification of the serum creatinine requirement seem justified. 相似文献
30.
Bernice Scholten Laura Guerrero Simn Shaji Krishnan Roel Vermeulen Anjoeka Pronk Benjamin M. Gyori John A. Bachman Jelle Vlaanderen Rob Stierum 《Environmental health perspectives》2022,130(3)
Background: Mechanistic data is increasingly used in hazard identification of chemicals. However, the volume of data is large, challenging the efficient identification and clustering of relevant data.Objectives: We investigated whether evidence identification for hazard assessment can become more efficient and informed through an automated approach that combines machine reading of publications with network visualization tools.Methods: We chose 13 chemicals that were evaluated by the International Agency for Research on Cancer (IARC) Monographs program incorporating the key characteristics of carcinogens (KCCs) approach. Using established literature search terms for KCCs, we retrieved and analyzed literature using Integrated Network and Dynamical Reasoning Assembler (INDRA). INDRA combines large-scale literature processing with pathway databases and extracts relationships between biomolecules, bioprocesses, and chemicals into statements (e.g., “benzene activates DNA damage”). These statements were subsequently assembled into networks and compared with the KCC evaluation by the IARC, to evaluate the informativeness of our approach.Results: We found, in general, larger networks for those chemicals which the IARC has evaluated the evidence to be strong for KCC induction. Larger networks were not directly linked to publication count, given that we retrieved small networks for several chemicals with little support for KCC activation according to the IARC, despite the significant volume of literature for these specific chemicals. In addition, interpreting networks for genotoxicity and DNA repair showed concordance with the IARC KCC evaluation.Discussion: Our method is an automated approach to condense mechanistic literature into searchable and interpretable networks based on an a priori ontology. The approach is no replacement of expert evaluation but, instead, provides an informed structure for experts to quickly identify which statements are made in which papers and how these could connect. We focused on the KCCs because these are supported by well-described search terms. The method needs to be tested in other frameworks as well to demonstrate its generalizability. https://doi.org/10.1289/EHP9112 相似文献