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1.
Srdan Verstovsek MD PhD Jean-Jacques Kiladjian MD PhD Alessandro M. Vannucchi MD Ruben A. Mesa MD FACP Peg Squier MD PhD J. E. Hamer-Maansson MSPH Claire Harrison MD 《Cancer》2023,129(11):1681-1690
Background
In a pooled analysis of the phase 3 Controlled Myelofibrosis Study With Oral JAK Inhibitor Treatment I (COMFORT-I) and COMFORT-II clinical trials, adult patients with intermediate-2 or high-risk myelofibrosis who received oral ruxolitinib at randomization or after crossover from placebo or best available therapy (BAT) had improved overall survival (OS).Methods
This post hoc analysis of pooled COMFORT data examined relevant disease outcomes based on the disease duration (≤12 or >12 months from diagnosis) before ruxolitinib initiation.Results
The analysis included 525 patients (ruxolitinib: ≤12 months, n = 84; >12 months, n = 216; placebo/BAT: ≤12 months, n = 66; >12 months, n = 159); the median age was 65.0–70.0 years. Fewer thrombocytopenia and anemia events were observed among patients who initiated ruxolitinib treatment earlier. At Weeks 24 and 48, the spleen volume response (SVR) was higher for patients who initiated ruxolitinib earlier (47.6% vs. 32.9% at Week 24, p = .0610; 44.0% vs. 26.9% at Week 48, p = .0149). In a multivariable analysis of factors associated with spleen volume reduction, a logistic regression model that controlled for confounding factors found that a significantly greater binary reduction was observed among patients with shorter versus longer disease duration (p = .022). At Week 240, OS was significantly improved among patients who initiated ruxolitinib earlier (63% [95% CI, 51%‒73%] vs. 57% [95% CI, 49%‒64%]; hazard ratio, 1.53; 95% CI, 1.01‒2.31; p = .0430). Regardless of disease duration, a longer OS was observed for patients who received ruxolitinib versus those who received placebo/BAT.Conclusions
These findings suggest that earlier ruxolitinib initiation for adult patients with intermediate-2 and high-risk myelofibrosis may improve clinical outcomes, including fewer cytopenia events, durable SVR, and prolonged OS.Plain Language Summary
- Patients with myelofibrosis, a bone marrow cancer, often do not live as long as the general population. These patients may also have an enlarged spleen and difficult symptoms such as fatigue.
- Two large clinical trials showed that patients treated with the drug ruxolitinib lived longer and had improved symptoms compared to those treated with placebo or other standard treatments.
- Here it was examined whether starting treatment with ruxolitinib earlier (i.e., within a year of diagnosis) provided benefits versus delaying treatment.
- Patients who received ruxolitinib within a year of diagnosis lived longer and experienced fewer disease symptoms than those whose treatment was delayed.
2.
3.
We conducted a double blind controlled trial in 28 Duchenne muscular dystrophy (DMD) patients with Deflazacort (DF), an oxazoline derivative of prednisolone which reduces its side-effects. Myometric muscle strength measurements, Scott Score and timed tests showed statistically significant improvement for the treated group (P less than 0.05). Side-effects after 9 months of treatment included mild cushingoid appearance in four patients (28%) and moderate in only one (7%), increased appetite in seven (50%), increased body hair in four (28%), irritability and hyperactivity in three (21%). Increased body weight was not prominent and was controlled with dietary measures. No patient had to be withdrawn from medication. More research and long-term follow-up are needed in order to establish the mechanism of improvement and the consequences of long-term steroid administration in DMD. In this regard DF appears as an alternative to prednisone preserving its benefits but with fewer side-effects. 相似文献
4.
Ruben A. Mesa MD Alfonso Quintás-Cardama MD Srdan Verstovsek MD PhD 《Current hematologic malignancy reports》2007,2(1):25-33
Myelofibrosis with myeloid metaplasia (MMM) is currently classified as a classic (ie, BCR-ABL-negative) myeloproliferative
disorder characterized by anemia, multiorgan extramedullary hematopoiesis, constitutional symptoms, and premature death from
either leukemic transformation or other disease complications. Stem cell transplantation can be curative, but many patients
either are not appropriate candidates or do not choose to accept the significant risks associated with transplantation. Current
pharmacologic therapy has been beneficial mainly in terms of palliating disease-associated cytopenias, constitutional symptoms,
splenomegaly, and other organ damage from excess myeloproliferation. Novel treatment strategies are under investigation, including
targeted inhibition of JAK2V617F, the activating tyrosine kinase point mutation present in about half of patients with MMM. In this article, we review both
the old and new pharmacologic options for MMM. 相似文献
5.
A López Granados M Anguita Sánchez M D Mesa Rubio M Franco Zapata R Vivancos Delgado G Bueno Ferrer J Suárez de Lezo F Vallés Belsúe 《Revista espa?ola de cardiología》1991,44(3):210-212
Almost 90% of primary acute pericarditis are idiopathic. Between specifics forms, a very low percentage of cases are due to chronic rheumatic diseases. A case of adult Still's disease (juvenile chronic rheumatoid arthritis) with acute pericarditis being the first clinical manifestation (besides fever and general syndrome) is presented. Therapy with oral prednisone was rapidly effective, and pericardial effusion resolved after 3 weeks of treatment, as echocardiography showed. 相似文献
6.
J Segura M Anguita D Mesa E Romo R Vivancos J Suárez de Lezo F Vallés 《Revista espa?ola de cardiología》1991,44(9):625-627
The case of a patient in whom acute pericarditis was the initial manifestation of an idiopathic hypereosinophilia is reported. Endomyocardial abnormalities were not found by echocardiography. Response to prednisone therapy was good; symptoms, pericardial effusion and eosinophilia early disappeared after therapy. Some clinical aspects of this uncommon disease are discussed. 相似文献
7.
M D Mesa M Anguita A López-Granados R Vivancos J Suárez de Lezo F Vallés G Bueno 《Revista espa?ola de cardiología》1991,44(5):347-350
Two cases of digitalis toxicity due to uncontrolled ingestion of medicinal herbs are presented. The first of them was caused by oleander (Nerium oleander); digoxinemia levels were very high in this patient (4.44 ng/l), who presented many brady- and tachyarrhythmias. These arrhythmias disappeared when digoxinemia returned to normal values. The second patient had atrial fibrillation with slow ventricular rate, severe hypokalemia (2.1 mEq/l) and normal digoxinemia levels. He was taking medicinal herbs for a cold, with sorbitol between its components. Sorbitol may be similar to mannitol and glycerol (osmotic diuretic drugs) when taken at high doses. Uncontrolled ingestion of medicinal herbs is not safe, and severe poisoning can occur. 相似文献
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9.
Johnson TS Xu JW Zaporojan VV Mesa JM Weinand C Randolph MA Bonassar LJ Winograd JM Yaremchuk MJ 《Tissue engineering》2004,10(9-10):1308-1315
Articular chondrocytes can synthesize new cartilaginous matrix in vivo that forms functional bonds with native cartilage. Other sources of chondrocytes may have a similar ability to form new cartilage with healing capacity. This study evaluates the ability of various chondrocyte sources to produce new cartilaginous matrix in vivo and to form functional bonds with native cartilage. Disks of articular cartilage and articular, auricular, and costal chondrocytes were harvested from swine. Articular, auricular, or costal chondrocytes suspended in fibrin glue (experimental), or fibrin glue alone (control), were placed between disks of articular cartilage, forming trilayer constructs, and implanted subcutaneously into nude mice for 6 and 12 weeks. Specimens were evaluated for neocartilage production and integration into native cartilage with histological and biomechanical analysis. New matrix was formed in all experimental samples, consisting mostly of neocartilage integrating with the cartilage disks. Control samples developed fibrous tissue without evidence of neocartilage. Ultimate tensile strength values for experimental samples were significantly increased (p < 0.05) from 6 to 12 weeks, and at 12 weeks they were significantly greater (p < 0.05) than those of controls. We conclude that articular, auricular, and costal chondrocytes have a similar ability to produce new cartilaginous matrix in vivo that forms mechanically functional bonds with native cartilage. 相似文献
10.
Fishery products are the main source of dietary n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA). Following the European Commission’s request to address the risks and benefits of seafood consumption, and taking into account the great variability of nutrient and contaminant levels in fishery products, the present work aims to estimate the n-3 LC-PUFA provided per serving of selected fishes, shrimps and mollusks that are commonly consumed in Spain. This would enable the establishment of a risk–benefit analysis of fish consumption and provide recommendations for fish intake to comply with nutritional guidelines of n-3 LC-PUFA intake. We confirmed high variation in the pattern and contents of fatty acids for different species. n-6 PUFA were minor fatty acids, whereas palmitic (C16:0), oleic (C18:1 n-9), and mainly eicosapentaenoic (C20:5 n-3) and docosahexaenoic (C22:6 n-3) acids were the major fatty acids in the sample. Therefore, consumption of 2–3 servings per week of a variety of fishery products may contribute to compliance with the recommended daily n-3 LC-PUFA intake while maintaining an adequate balance to avoid contaminant-derived potential risks (metals and others). Taking the fatty acid content of fishery products described in this study into consideration, it is advisable to include one serving of fatty fish per week in order to meet recommended n-3 LC-PUFA levels. 相似文献