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11.
《Expert Review of Clinical Immunology》2013,9(6):849-852
Evaluation of: Tashkin, Elashoff, Clements PJ et al. Cyclophosphamide versus placebo in scleroderma lung disease. N. Engl. J. Med. 354(25), 2655–2666 (2006).Interstitial lung disease has become one of the leading causes of morbidity and mortality in systemic sclerosis. Currently, there remains a void in proven effective treatment strategies to provide clinical benefit to affected patients. The article under evaluation pioneers the efforts of investigating oral cyclophosphamide in treating scleroderma lung disease by designing a prospective, double-blinded, placebo-controlled study examining the drug’s effect on outcome measures of forced vital capacity, patient subjective health assessment questionnaire disability scores, among others. We review the methods, results and overall conclusion of the study, which shows a significant, yet modest, result demonstrating the benefit of oral cyclophosphamide in the context of this disease setting. We conclude that although the study provides an excellent starting point for examining the efficacy of cyclophosphamide in certain forms of scleroderma lung disease, the study’s high drop-out rate, choice of forced vital capacity as a primary outcome, side-effect profile of the drug and overall significance of the results make the conclusions difficult to incorporate into clinical practice. 相似文献
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《Expert opinion on emerging drugs》2013,18(2):173-179
Introduction: Scleroderma is an often-fatal autoimmune connective tissue disease. Recommendations for treating digital ulcers and pulmonary hypertension in scleroderma have recently been established by the European League Against Rheumatism. Conversely, although many valuable insights have been generated into the molecular mechanism underlying the persistent fibrotic phenotype in scleroderma, no safe, clinically proven effective treatment has been found for this aspect of the disease. Areas covered: Recent evidence suggests that, based on genome-wide molecular profiling, scleroderma can be loosely divided into ‘fibroproliferative' and ‘inflammatory' cohorts. The latter cohort contains patients with localized and ‘limited' disease, as well as a small subset of those with ‘diffuse' disease. Drugs targeting either B cells or ILs might be useful to treat patients who possess an ‘inflammatory' gene expression signature. Expert opinion: In the future, a ‘personalized medicine' approach might be used to treat patients with scleroderma: individuals with an ‘inflammatory' gene expression signature may be successfully treated with drugs specifically targeting the immune system. Indeed, drugs currently approved for other rheumatic disease might also be used to treat scleroderma patients bearing an ‘inflammatory' gene expression profile. 相似文献
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Eiji MUROI Fumihide OGAWA Toshifumi YAMAOKA Fumiko SUEYOSHI Shinichi SATO 《The Journal of dermatology》2010,37(1):81-84
We report a 4-year-old girl presenting with progressive linear scleroderma affecting the right leg. Biopsy specimen disclosed typical histopathological findings of localized scleroderma. Right leg magnetic resonance imaging (MRI) showed high signal areas on T2 -weighted images on the subcutaneous fatty tissue, muscles and bone marrow, suggesting that skin inflammation extended to the bone marrow. Oral corticosteroid therapy was instituted with improvement of both skin sclerosis and MRI findings. Our observations suggest that MRI examination should be considered in patients with localized scleroderma to evaluate the extension of the inflammation. 相似文献
16.
Dominique Lacroix Fran?ois Brigadeau Christelle Marquié Didier Klug 《Europace : European pacing, arrhythmias, and cardiac electrophysiology》2004,6(4):336-342
Two cases of systemic sclerosis with sustained ventricular tachycardia (VT) are presented. The first patient received hydroxychloroquine for skeletal muscle disease coexisting with cardiac involvement. In both cases, 3D-electroanatomic mapping showed low-voltage areas in the right ventricle. In the first patient the tachycardia was mapped and a protected isthmus suggesting reentry was delineated and ablated. Other substrate locations were indirectly identified by pacemapping on the right and left ventricular endocardium in the second patient. VT did not reoccur during follow-up. Radiofrequency catheter ablation is safe and effective and electroanatomic mapping may be helpful in patients with systemic sclerosis. 相似文献
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Camille Daste François Rannou Luc Mouthon Katherine Sanchez Alexandra Roren Vincent Tiffreau Éric Hachulla Philippe Thoumie Jean Cabane Emmanuel Chatelus Jean Sibilia Serge Poiraudeau Christelle Nguyen 《Seminars in arthritis and rheumatism》2019,48(4):694-700
Background
To estimate patient acceptable symptom state (PASS) and minimal clinically important difference (MCID) for patient-reported outcomes in systemic sclerosis (SSc).Methods
We conducted a secondary analysis of the SCLEREDUC trial, a 12-month randomized controlled trial comparing the efficacy of physical therapy to usual care in 220 SSc patients followed-up from September 2005 to October 2010. Self-rated state and change in patient health at 12 months were assessed by using 2 external anchors extracted from the Medical Outcomes Study 36-Item Short-Form. Patients who self-rated their health as “excellent”, “very good” or “good” were the PASS group and those who self-rated their health change as “somewhat better” were the MCID group. Main outcomes were the estimates of PASS by using the 75th percentile method and of MCID by using the mean change in scores method for pain and activity limitation.Results
PASS (95% confidence interval) and mean (SD) MCID estimates at 12 months were 53.75 (34.00 to 68.00) and ?6.74 (32.02) for the joint-pain visual analog scale (range 0–100), 1.41 (1.13 to 1.63) and ?0.21 (0.48) for the Health Assessment Questionnaire (HAQ, range 0–3), 1.27 (1.07 to 1.62) and ?0.13 (0.45) for the scleroderma HAQ (range 0–3), 26.00 (17.00 to 37.00) and -3.38 (9.87) for the Cochin Hand Function Scale (range 0–90), and 19.40 (17.20 to 21.90) and ?5.69 (6.79) for the McMaster-Toronto Arthritis Patient Preference Disability Questionnaire (range 0–30), respectively.Conclusions
We provide, for the first time, the PASS and MCID estimates for pain and activity limitation in SSc.18.
目的 建立硬皮病伴发肺间质病变(systemic scleroderma associated with interstitial lung disease,Ssc-ILD)的小鼠动物模型,并初步探讨其发病机制。 方法 造模组以0.4 mg/mL浓度博来霉素(bleomycin,BLM)背部中央区域局部皮下注射0.1 mL/天,连续28天;对照组以PBS缓冲液(pH=7.4)相同方法处理;连续观察2组小鼠大体形态变化,以HE和Masson染色明确模型的可靠性,通过检测羟脯氨酸了解纤维化程度,并通过免疫组化检测TGF-β1、α-SMA、collagen-1、MMP-9、CD8+T细胞、CD68+巨噬细胞、IL-23的表述。 结果 造模组小鼠皮肤显著硬化,镜下真皮层显著增厚,胶原纤维束增多,排列紧密,胶原含量升高,符合硬皮病表现;并且肺组织出现明显炎症和纤维化,胶原含量显著升高,免疫组化检测发现TGF-β1、collagen-1、MMP-9、α-SMA、CD8+T细胞、CD68+巨噬细胞、IL-23的表达均显著性增高(P均<0.05)。 结论 C3H/He小鼠连续28天皮下注射0.4 mg/mL的BLM能诱导Ssc-ILD动物模型,出现符合Ssc标准的皮肤改变,肺部出现明显的炎症和纤维化,与TGF-β1升高密切相关,并伴随α-SMA、collagen-1、MMP-9、CD8+T细胞、CD68+巨噬细胞、IL-23增多。 相似文献
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Tatsuya Shimizu Chie Saito Megumi Watanabe Ryota Ishii Tetsuya Kawamura Kei Nagai Akiko Fujita Shuzo Kaneko Hirayasu Kai Naoki Morito Joichi Usui Masahiro Yokosawa Yuya Kondo Sae Inoue Naoko Okiyama Kunihiro Yamagata 《Internal medicine (Tokyo, Japan)》2021,60(7):1101
A 40-year-old Japanese woman developed malignant-phase hypertension complicated by thrombotic microangiopathy, progressing to end-stage renal disease. Five years later, she was diagnosed with pulmonary arterial hypertension and interstitial pneumonia. Despite a lack of overt skin sclerosis, nucleolar staining in our indirect immunofluorescence analysis and nailfold capillaroscopy facilitated the diagnosis of anti-PM/Scl antibody-positive systemic sclerosis. We observed the persistent presence of anti-PM/Scl antibodies throughout the clinical course, suggesting that her kidney disease was scleroderma renal crisis. Anti-PM/Scl antibodies can be associated with multiple organ diseases. Careful attention to a patient''s antinuclear antibody pattern and dermatological findings may help clarify the etiology of undiagnosed diseases. 相似文献