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51.
S. Vincent Rajkumar 《American journal of hematology》2014,89(10):998-1009
Disease overview : Multiple myeloma accounts for approximately 10% of hematologic malignancies. Diagnosis : The diagnosis requires 10% or more clonal plasma cells on bone marrow examination or a biopsy proven plasmacytoma plus evidence of associated end‐organ damage. If end‐organ damage is not present, the presence of 60% or more clonal plasma cells in the marrow is also considered as myeloma. Risk stratification : In the absence of concurrent trisomies, patients with 17p deletion, t(14;16), and t(14;20) are considered to have high‐risk myeloma. Patients with t(4;14) translocation are considered intermediate‐risk. All others are considered as standard‐risk. Risk‐adapted intial therapy : Standard‐risk patients can be treated with lenalidomide plus low‐dose dexamethasone (Rd), or a bortezomib‐containing triplet such as bortezomib, cyclophosphamide, dexamethasone (VCD). Intermediate‐risk and high‐risk patients require a bortezomib‐based triplet regimen. In eligible patients, initial therapy is given for approximately 4 months followed by autologous stem cell transplantation (ASCT). Standard risk patients can opt for delayed ASCT if stem cells can be cryopreserved. In patients who are not candidates for transplant, initial therapy is given for approximately 12 to 18 months. Maintenance therapy : After initial therapy, lenalidomide maintenance is considered for standard risk patients who are not in very good partial response or better, while maintenance with a bortezomib‐based regimen should be considered in patients with intermediate or high risk myeloma. Management of refractory disease : Patients with indolent relapse can be treated first with 2‐drug or 3‐drug combinations. Patients with more aggressive relapse often require therapy with a combination of multiple active agents. Am. J. Hematol. 89:998–1009, 2014. © 2014 Wiley Periodicals, Inc. 相似文献
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Andrew Crawford Shareefa Dalvie Sarah Lewis Anthony King Israel Liberzon George Fein Karestan Koenen Rajkumar Ramesar Dan J. Stein 《Metabolic brain disease》2014,29(2):333-340
Alcohol dependence (AD) has a large heritable component. Genetic variation in genes involved in the absorption and elimination of ethanol have been associated with AD. However, some of these polymorphisms are not present in an African population. Previous studies have reported that a type of AD which is characterized by anxious behaviour may be a genetically specific subtype of AD. We investigated whether variation in genes encoding cytochrome P450 2E1 (CYP2E1) or acetaldehyde-metabolising enzymes (ALDH1A1, ALDH2) might alter the risk of AD, with and without symptoms of anxiety, in a Cape population with mixed ancestry. Eighty case control pairs (one with AD, one without AD) were recruited and individually matched for potential confounders. Genotype data were available for 29 single-nucleotide polymorphisms (SNPs) across the three genes. Linkage disequilibrium D′ values were evaluated for all pairwise comparisons. Allele and haplotype frequencies were compared between cases and controls using a χ 2 test. The ACAG haplotype in block 4 of the ALDH1A1 gene provided evidence of an association with AD (p?=?0.03) and weak evidence of an association with AD without symptoms of anxiety (p?=?0.06). When a genetic score was constructed using SNPs showing nominal evidence of association with AD, every extra risk allele increased the odds of AD by 35 % (OR 1.35, 95%CI 1.08, 1.68, p?=?0.008) and the odds of having AD with anxiety symptoms increased by 53 % (OR 1.53, 95%CI 1.14, 2.05, p?=?0.004). Although our results are supported by previous studies in other populations, they must be interpreted with caution due to the small sample size and the potential influence of population stratification. 相似文献
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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
54.
Deepak Shivanna Dayanand Manjunath Rajkumar Amaravathi 《Journal of hand and microsurgery》2014,6(2):69-73
Dislocations and fracture dislocations of carpal bones are uncommon injuries which invariably poses challenges in the management. Perilunate fracture dislocations are the combination of ligamentous and osseous injury that involve the “greater arc” of the perilunate associated instability. Despite their severity, these injuries often go unrecognized in the emergency department leading to delayed diagnosis and treatment. A Prospective study was done from June 2008 to December 2013 in 15 cases of complex wrist injuries which included of greater arch injuries, perilunate fracture dislocation and one dorsal dislocation of Scaphoid. 10 cases of perilunate fracture dislocation underwent open reduction and internal fixation with Herbert screw and k-wire, 4 cases of greater arch injury underwent closed reduction and kwire fixation and one case of neglected dorsal dislocation underwent proximal row carpectomy. One patient had Sudecks osteodystrophy 1 had Scaphoid nonunion and 6 had median nerve compression. Overall outcome according to Mayo wrist score was 53 % excellent, 33 % good and 14 % fair. Greater arch injuries are difficult to treat because injuries to many ligaments are involved and failure to recognize early leads to persistent pain, disability and early onset of arthritis. Prompt recognition requires CT scan and MRI. Management requires reduction and multiple K-Wiring according to merits of the case. 相似文献
55.
Chandramohan Eaga Shivakumar Mantri Rajkumar Malayandi Phani Krishna Kondamudi Sumon Chakraborty S. V. N. Raju Deepika Aggarwal 《Journal of Pharmaceutical Investigation》2014,44(3):197-204
The objective of current study was to develop metformin hydrochloride modified release small sized tablets, and to evaluate its bioequivalence when compared with the reference product (Glucophage® SR). The physicochemical properties of the formulated and reference tablets were determined and compared. The in vitro dissolution profiles of formulated tablets were obtained using bio-relevant media and IVIVC was established. Bioequivalence investigation was carried out in 32 healthy male volunteers who received a single dose 1,000 mg of both test and reference products in a randomized two-way crossover design in postprandial conditions. After dosing, serial blood samples were collected for a period of 48 h. Metformin concentration was assayed by using a validated LC–MS/MS method. The log-transformed Cmax and AUC were statistically compared by analysis of variance, and the 90 % confidence intervals (CI) of the ratio of the log-transformed Cmax and AUC between the most promising developed formulation and the reference product were determined. It was deduced that the dissolution rate profile of the formulated modified release small sized tablets was similar to the reference product employed in the study. Their similarity and difference factors were found to be well within the established limits. In the bioequivalence study, the difference in Cmax, AUClast and AUCinf between the test and reference product was not statistically significant, with the 90 % CI of 100.73–116.20, 86.16–97.37 and 87.12–96.99 %, respectively. The results suggested that the metformin small tablets formulated with reduced quantity of controlled release polymer were found to be bioequivalent in the postprandial state. For these small tablets, pH 5.5 acetate buffer as a bio-relevant dissolution media for the development of IVIVC. 相似文献
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Laura Heathfield Miguel Lacerda Christel Nossek Lisa Roberts Rajkumar S Ramesar 《European journal of human genetics : EJHG》2013,21(10):1190-1176
Stargardt disease is an ABCA4-associated retinopathy, which generally follows an autosomal recessive inheritance pattern and is a frequent cause of macular degeneration in childhood. ABCA4 displays significant allelic heterogeneity whereby different mutations can cause retinal diseases with varying severity and age of onset. A genotype–phenotype model has been proposed linking ABCA4 mutations, purported ABCA4 functional protein activity and severity of disease, as measured by degree of visual loss and the age of onset. It has, however, been difficult to verify this model statistically in observational studies, as the number of individuals sharing any particular mutation combination is typically low. Seven founder mutations have been identified in a large number of Caucasian Afrikaner patients in South Africa, making it possible to test the genotype–phenotype model. A generalised linear model was developed to predict and assess the relative pathogenic contribution of the seven mutations to the age of onset of Stargardt disease. It is shown that the pathogenicity of an individual mutation can differ significantly depending on the genetic context in which it occurs. The results reported here may be used to identify suitable candidates for inclusion in clinical trials, as well as guide the genetic counselling of affected individuals and families. 相似文献