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151.
Anne M. Connolly Richard M. Keeling Shobhna Mehta Alan Pestronk Joshua R. Sanes 《Neuromuscular disorders : NMD》2001,11(8)
To optimize and evaluate treatments for muscular dystrophy, it is important to know the natural history of the disease in the absence of therapeutic intervention. Here we characterized disease progression of three mutant mouse strains of muscular dystrophy: mdx mice, which lack dystrophin; mdx:utrn−/− mice, which also lack utrophin; and dy/dy mice, which are deficient in laminin α2. Normal mice show a marked increase in forelimb strength over the first 10 weeks of life and little fatigue (<5%) over five consecutive strength trials. Mdx and mdx:utrn−/− mice demonstrate less strength then normal mice and approximately 40% fatigue at each age. Mdx mice become obese but mdx:utrn−/− mice do not. Dy/dy mice remain small and are much weaker than mdx and mdx:utrn−/− mice at all ages even when normalized to weight; however, they show only minimal fatigue (10%). This work demonstrates a distinct pattern of disease progression in each model and provides a foundation for assessing strategies for improving strength in each model. 相似文献
152.
Ewa Moric-Janiszewska Grazyna Markiewicz-Loskot 《Europace : European pacing, arrhythmias, and cardiac electrophysiology》2007,9(5):259-266
Arrhythmogenic right ventricular dysplasia (ARVD) is a clinical and pathologic entity whose diagnosis rests on electrocardiographic and angiographic criteria; pathologic findings, replacement of ventricular myocardium with fatty and fibrous elements, preferentially involve the right ventricular (RV) free wall. There is a familial occurrence in about 50% of cases, with autosomal dominant inheritance with variable penetrance and polymorphic phenotypic expression, and is one of the major genetic causes of juvenile sudden death. When the dysplasia is extensive, it may represent the extensive form of ARVCM (arrhythmogenic right ventricular cardiomyopathy). In this review, we focus on the some candidate genes mutations and information on some genotype-phenotype correlation in the ARVD. Our findings are in agreement with those of European Society of Cardiology who stated that: genetic analysis is usefull in families with RV cardiomyopathy because whenever a pathogenetic mutation is identified, it becomes possible to establish a presymptomatic diagnosis of the disease among family members and to provide them with genetic counseling to monitor the development of the disease and to assess the risk of transmitting the disease offspring. On the basis of current knowledge, genetic analysis does not contribute to risk stratification of arrhythmogenic RV cardiomyopathy. 相似文献
153.
整合素α6在肝窦毛细血管化中的表达 总被引:5,自引:0,他引:5
目的探讨整合素α6在肝窦毛细血管化时的表达情况. 方法皮下注射四氯化碳制备大鼠肝纤维化模型,进行层粘连蛋白(LN)及其整合素受体α6免疫组织化学检测及整合素α6斑点免疫印迹研究. 结果动态观察了LN在肝纤维化时沿肝窦在Disse间隙沉积形成肝窦毛细血管化;正常时整合素α6局限于汇管区血管内皮和胆管内皮细胞膜上,窦内皮细胞(SEC)上无表达,肝窦毛细血管化时,SEC出现整合素α6阳性表达沿肝窦连续分布,整合素α6在纤维化时组织中含量明显高于正常(P<0.05). 结论肝窦毛细血管化时SEC出现整合素α6亚基的诱导表达. 相似文献
154.
糖尿病视网膜病变与血清Ⅳ型胶原和层粘连蛋白以及粘附分子变化的相关性 总被引:1,自引:0,他引:1
目的 探讨糖尿病视网膜病变不同时期细胞外间质、血管基膜成分以及血管内皮细胞粘附分子在血循环中的变化,了解他们与血管基膜和血管内皮细胞损伤的相关性。方法 85例(男40例、女45例)2型糖尿病患者分无视网膜病变(NDR)组31例、背景期视网膜病变(BDR)组24例和增殖期视网膜病变(PDR)组30例,采用放射免疫法和ELISA法测其血清Ⅳ型胶原(ⅣC)、层粘蛋白(LN)和血管内皮细胞粘附分子(sVCAM—1)含量,同时设健康体检者20人为对照组。结果 三组糖尿病患者血清LN、ⅣC、sVCAM—1水平均高于对照组。PDR组的血清LN、ⅣC和sVCAM—1水平与对照组比较,差异有非常显著意义(P<0.01),与NDR组比较,差异也有非常显著意义(P<0.01);BDR组血清LN、ⅣC和sVCAM—1水平与对照组比较,差异有非常显著意义(P<0.01);BDR组血清LN、ⅣC和sVCAM—1水平与对照组比较,差异有非常显著意义(P<0.01);PDR组与BDR组比较,仅LN、ⅣC差异有非常显著意义(P<0.01);BDR组与NDR组比较,仅sVCAM—1差异有显著意义(P<0.05)。三组糖尿病患者血清三项指标之间无相关性(分别为r=0.119,r=0.167和r=-0.210;P>0.05)。结论 血清ⅣC、LN和sVCAM—1用于联合检测,能较好地反映糖尿病微血管病变的发展过程,为其早期诊断和治疗提供依据,也可作为糖尿病视网膜病变严重程度的估计和预后判断的指标。 相似文献
155.
整合素β1亚单位对肝癌细胞与层黏连蛋白趋化行为的影响 总被引:1,自引:0,他引:1
目的 研究整合素β1亚单位对肝癌细胞与层黏连蛋白(LN)趋化行为的影响。方法 采用双微吸管实验法进行肝细胞癌(HCC)细胞趋化实验,在两侧微管内加入相同浓度(50μg/ml,200μg/m1)的LN,并引导微管尖端与同-HCC细胞紧密接触,动态观察细胞两侧伪足形成过程;当两侧微管LN浓度为200μg/ml,在一侧微吸管内加入针对整合素β1亚单位(CD29)的单克隆抗体(Anti—CD29)20μg/m1,考察β1整合素亚单位阻断对HCC细胞伪足形成的影响。利用流式细胞仪对Hcc细胞表面整合素β1亚单位的表达进行分析。结果 两侧微吸管加入相同浓度的LN,细胞向两侧微吸管两侧均有伪足形成;随作微吸管内LN浓度的增加,细胞伪足增加,且两侧微吸管内伪足的变化基本呈对称性;在此基础上,微吸管加入Anti—CD29的一侧,HCC细胞伪足生长曲线呈现明显的抑制,而未加入Anti—CD29的微吸管一侧与加入的对侧相比,该侧细胞的伪足明显增加。流式细胞仪分析表明,所研究细胞整合素β1亚单位表达率达95.78%。结论 整合素β1亚单位是联系HCC细胞与HCC细胞对LN趋化性伪足形成的重要受体基础。 相似文献
156.
Yoshikawa M Tsuji N Shimomura Y Hayashi H Ohgushi H 《Calcified tissue international》2008,83(2):139-145
The effect of the configuration of porous cylindrical hydroxyapatite (HA) scaffold and laminin preparation of the scaffold on bone formation was estimated. HA scaffolds with a hollow center of 2 or 4 mm in diameter and those without a hollow center were used. The scaffolds were immersed in laminin solution or in culture medium. Bone marrow cells were obtained from the femora of male Fischer 344 rats. Cell suspension was prepared at 1 x 10(6) cells/mL density. The cells were seeded into HA scaffolds. Each scaffold was implanted in the dorsal subcutis of rats for 4 weeks. Bone formation in scaffolds was observed histologically. The quantity of osteocalcin was measured immunochemically. Many pores containing bone were identified in the laminin-immersed HA scaffold with a hollow center measuring 4 mm in diameter than those without and those with a hollow center measuring 2 mm in diameter. A greater quantity of osteocalcin was detected in the HA scaffold with immersion in laminin than in that without immersion in laminin. However, the results of the immunochemical assay for osteocalcin showed that a hollow center in the scaffold did not contribute to bone formation compared to scaffolds without a hollow center. It is considered that laminin may act as an adhesive for effective cell attachment to the walls of the pores in an HA scaffold. 相似文献
157.
BACKGROUND: Platelet hyperactivity plays an important role in atherosclerosis and arterial thrombosis. Artemisia dracunculus L. (tarragon) is a common table vegetable all over Iran and known for its anticoagulant activity in Iranian folk medicine. OBJECTIVE: The present study was undertaken to investigate the effect of Artemisia dracunculus leaves methanol crude extract and its chloroform fraction on platelet aggregation, secretion and adhesion to laminin coated plates. MATERIALS AND METHODS: Human platelets were incubated with different concentrations of the test sample (equivalent to 25-200 mug of plant leaves powder/ml). The treated and untreated platelets were then activated with thrombin and adhesion to the laminin coated plates were evaluated. RESULTS: Based on our observations, the methanol extract and its chloroform fraction, at a concentration of 200 mug/ml, inhibited platelet adhesion to laminin coated wells by 50% and 60%, respectively. In addition to alternation of cell adhesive properties, protein secretion and self aggregation of the treated platelets were decreased upon treatment with the crude extract and its chloroform fraction. CONCLUSIONS: Our results showed that the methanol crude extract and chloroform fraction of tarragon could inhibit platelets adhesion, aggregation and secretion. These findings provide scientific basis for the traditional use of tarragon as a blood-diluting factor, as locally called, or as an anticoagulant. 相似文献
158.
基底膜是一种维持器官正常结构及功能的特殊的细胞外基质,是上皮组织与基底膜结缔组织间的屏障,肿瘤侵袭、发展、恶变时首先要穿越突破基底膜。肿瘤组织的微血管密度能定量的反应出肿瘤血管的生长情况,进而可预示肿瘤生长、转移及复发的趋势。本文就LN的结构功能,MVD及预后功能及二者与实体瘤的关系等作一综述。 相似文献
159.
Fatima Lekmine Hélène Feracci Gérard Milhaud Françoise Treilhou-Lahille N. Jeanne 《Virchows Archiv : an international journal of pathology》1999,434(4):325-332
Medullary thyroid carcinoma (MTC) originates from C cells, which secrete calcitonin (CT), their specific marker. C cells
are located in contact with the basement membrane (BM) of the thyroid follicles, which is partly made up of the laminin-2
isoform synthesized by thyrocytes. During oncogenesis, proliferation of the C cells, invading the centre of the follicles,
leads to a break in their normal contact with the BM. As specific interactions of cells with BM components, especially laminins,
are important for proliferation and differentiation, we investigated the relationships of normal and neoplastic C cells with
laminin in the Wag/Rij rat model of human MTC. Immunocytochemical studies showed a progressive loss of the laminin layer underlying
the hyperplastic C cell nodules around the large dedifferentiated tumours. The α2, β1 and γ1 chains of the laminin-2 isoform
were synthesized and secreted by rat MTC 6–23 cell cultures and the tumours induced by subcutaneous injection of these cells.
In situ hybridization combined with anti-CT immunocytochemistry showed a low expression of α2 mRNA on differentiated C cells
and thyrocytes, but an overexpression on immunonegative spontaneous MTC and induced intrathyroid tumours. The high level of
α2 gene expression, together with tumour dedifferentiation, suggests a relationship with malignancy.
Received: 6 October 1998 / Accepted: 10 November 1998 相似文献
160.
Loubna Hamza Silvia Castelli Stefano Cannata Paolo Luly Raffaele Petruzzelli 《Toxicon》2010,56(3):381-1794
The Macrovipera lebetina venom consists of a complex mixture of proteins belonging to a few main families according to their enzymatic and pharmacological activity. Given the serious pathophysiological effects caused by M. lebetina bites mainly induced by muscle degeneration, we decided to investigate the myotoxic activity of some venom fractions. In the present study we describe the purification and characterization of a 22.600 kDa protein, named in the following Mlp4.2, that shares myotoxic but not haemorrhagic activity in vivo. Herein we report that Mlp4.2 is a metalloproteinase belonging to the PI-SVMPS family able, in vitro, to proteolyse extracellular matrix proteins as laminin and fibronectin. Histological observations of mouse anterior tibialis Mlp4.2-treated muscle, demonstrate that this protein induces a massive degeneration of myofibers but not haemorrhage. The immunofluorescence analysis of protein-treated anterior tibialis, demonstrates that Mlp4.2 is able to disarray the laminin network surrounding muscle fibers. Finally Mlp4.2 did not show any direct cytolytic activity towards the myogenic cell line C2C12 in culture. The data reported herein suggest that the myotoxicity of Mlp4.2 is primarily linked to the disruption of the muscle fibers interaction with extracellular matrix proteins. 相似文献