首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   20319篇
  免费   1286篇
  国内免费   662篇
耳鼻咽喉   563篇
儿科学   402篇
妇产科学   244篇
基础医学   3104篇
口腔科学   827篇
临床医学   1506篇
内科学   2594篇
皮肤病学   319篇
神经病学   1077篇
特种医学   414篇
外国民族医学   4篇
外科学   2359篇
综合类   2709篇
现状与发展   1篇
预防医学   793篇
眼科学   1811篇
药学   2243篇
  7篇
中国医学   686篇
肿瘤学   604篇
  2024年   46篇
  2023年   249篇
  2022年   534篇
  2021年   766篇
  2020年   571篇
  2019年   530篇
  2018年   553篇
  2017年   518篇
  2016年   501篇
  2015年   594篇
  2014年   937篇
  2013年   1212篇
  2012年   927篇
  2011年   985篇
  2010年   944篇
  2009年   915篇
  2008年   952篇
  2007年   924篇
  2006年   840篇
  2005年   851篇
  2004年   714篇
  2003年   659篇
  2002年   557篇
  2001年   525篇
  2000年   402篇
  1999年   433篇
  1998年   423篇
  1997年   392篇
  1996年   323篇
  1995年   299篇
  1994年   285篇
  1993年   228篇
  1992年   249篇
  1991年   223篇
  1990年   203篇
  1989年   198篇
  1988年   179篇
  1987年   160篇
  1986年   149篇
  1985年   223篇
  1984年   187篇
  1983年   132篇
  1982年   182篇
  1981年   142篇
  1980年   124篇
  1979年   80篇
  1978年   72篇
  1977年   60篇
  1976年   43篇
  1975年   23篇
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
1.

Background

Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.

Objectives

To investigate the molecular mechanism by which botulinum toxin improves rosacea lesions.

Methods

Primary human and murine mast cells were pretreated with onabotulinum toxin A or B or control. Mast cell degranulation was evaluated by β-hexosaminidase activity. Expression of botulinum toxin receptor Sv2 was measured by qPCR. The presence of SNAP-25 and VAMP2 was established by immunofluorescence. In vivo rosacea model was established by intradermally injecting LL-37 with or without onabotulinum toxin A pretreatment. Mast cell degranulation was assessed in vivo by histologic counts. Rosacea biomarkers were analyzed by qPCR of mouse skin sections.

Results

Onabotulinum toxin A and B inhibited compound 48/80-induced degranulation of both human and murine mast cells. Expression of Sv2 was established in mouse mast cells. Onabotulinum toxin A and B increased cleaved SNAP-25 and decreased VAMP2 staining in mast cells respectively. In mice, injection of onabotulinum toxin A significantly reduced LL-37-induced skin erythema, mast cell degranulation, and mRNA expression of rosacea biomarkers.

Conclusions

These findings suggest that onabotulinum toxin reduces rosacea-associated skin inflammation by directly inhibiting mast cell degranulation. Periodic applications of onabotulinum toxin may be an effective therapy for refractory rosacea and deserves further study.  相似文献   
2.
Objective: To report a case of labour induction during extracorporeal membrane oxygenation (ECMO) support in a patient with acute respiratory distress syndrome (ARDS) caused by influenza and review of the literature.

Methods: Case report and the literature search of all English articles on delivery while on ECMO in patients with ARDS caused by influenza.

Results: A 25-year-old pregnant woman was initiated with ECMO due to severe ARDS caused by influenza A (H1N1) virus. When the patient had symptoms of colporrhagia and uterine contractions, the medical team decided to start labour induction while on ECMO. There were in total five case reports identified. Maternal oxygenation was improved after delivery and ECMO was successfully discontinued.

Conclusions: Maternal oxygenation was improved after delivery, which may be beneficial to reduce the duration of ECMO. Caesarean section (CS) may be the most used mode and labour induction could be another option. The procedure should be performed by an experienced ECMO team, cooperating with the obstetrician, anaesthesiologist, and ICU doctors.  相似文献   

3.
BACKGROUND: Three dimensional skin equivalents are widely used in dermatopharmacological and toxicological studies and as autologous transplants in wound healing. In pharmacology, there is tremendous need for monitoring the response of engineered skin equivalents to external treatment. Transplantation of skin equivalents for wound healing requires careful verification of their quality prior to transplantation. Optical coherence tomography (OCT) is a non-contact, non-destructive imaging technique for living tissues offering the potential to fulfill these needs. This work presents an analysis of OCT for high-resolution monitoring of skin equivalents at different stages during the culture process. METHODS: We developed a high-resolution OCT imaging setup based on a commercially available OCT system. A broadband femtosecond laser light source replaces the original superluminescence diode. Tomograms of living skin equivalents were recorded with an axial resolution of 3 mum and correlated with histology and immunofluorescence images. Comparison with standard low-resolution OCT is presented to emphasize the advantages of high-resolution OCT for this application. RESULTS: OCT is particularly able to distinguish between different layers of skin equivalents including stratum corneum, epidermal and dermal layer as well as the basement membrane zone. The high-resolution OCT scans correlate closely with two key benchmarks, histology and immunofluorescence imaging. CONCLUSIONS: This study clearly demonstrates the benefits of high-resolution OCT for identifying living tissue structure and morphology. Compared with the current gold standard histology, OCT offers non-destructive tissue imaging, enabling high-resolution evaluation of living tissue morphology and structure as it evolves.  相似文献   
4.
The aim of this study was to design a new intravenous blood–gas exchange device and to estimate the design characteristics of the device with a dimensionless function by using a substance that can be used instead of bovine blood. In addition, the characteristics of oxygen transfer were estimated using empirical formulas and the reliability of the equations was ascertained by comparing their output with an experiment performed using bovine blood. The dimensionless function was derived using distilled water and bovine blood to estimate the oxygen transfer rate. Using the derived equations, the calculated oxygen transfer rates for bovine blood and distilled water were similar for Reynolds numbers ranging from 0.7 to 7.0. Therefore, it is possible to estimate the oxygen transfer rate in bovine blood, which is a non-Newtonian fluid, using distilled water, which is a Newtonian fluid. Moreover, it was possible to verify the related equations because the oxygen transfer rate could be estimated using the derived equations, according to the diameters of the various device modules.  相似文献   
5.
Several cell lines secreting monoclonal antibodies (Mabs) against a major forebrain synaptic membrane (SM) glycoprotein, gp 50, have been raised. Western blots show that the Mabs react with a polypeptide doublet of Mrs 49 and 45 kDa. These polypeptides exist solely in a concanavalin A (Con A) binding form. Removal of the Con A receptors by digestion with endo-beta-N-acetylglucosaminidase H (endo H) lowers the Mrs of the glycoprotein doublet to 36.5 and 34 kDa. Western blots of 2D polyacrylamide gels indicate that gp 50 exists in several isoforms. Solid phase radioimmunoassay (RIA) and Western blots of brain subcellular fractions show the antigenic material to be concentrated in the SM fraction, but to be present in much lower amounts in synaptic junctions and postsynaptic densities. Gp 50 appears to be brain specific. Regional distribution studies show that it is present in all brain regions but is two-fold concentrated in cerebellum, brainstem and midbrain compared to forebrain. Immunocytochemical studies of several brain regions show that gp 50-like immunoreactivity is neuron specific and is concentrated in selected neuronal species, particularly granule cells. In both cerebellar and hippocampal granule cells gp 50-like immunoreactivity is localized in the perikarya and primary dendrites. Though immunocytochemistry did not show staining of synaptic regions this may be due to masking of the reactive epitope. The results are discussed in terms of the molecular properties of gp 50 and its subcellular localization in brain tissue.  相似文献   
6.
The term synovial sarcoma was first proposed for the histologically well defined entity by Knox in 1936. The name was proposed due to the fact that at least the cases reported in the early part showed some resemblance of the tumour to normal synovial tissue histologically. Thereafter, tumours have been diagnosed from areas without synovial tissue. The diagnosis of monophasic tumours can be difficult and immunostains appear to be a good diagnostic tool in those cases. The occurrence in the mandible is extremely rare. This is a case of synovial sarcoma arising in the condyle involving most of the ramus. The tumour was diagnosed as synovial sarcoma with predominant spindle cell component by correlation of histopathology with immunostains (cytokeratin, epithelial membrane antigen, actin and desmin). The patient has been treated with surgery and radiotherapy.  相似文献   
7.
背景:组织工程是一个多学科研究的交叉学科,其目标是使人体损伤的组织和器官再生,通过这种假设,几乎所有的动物组织都可以在实验室进行培养。一般的方法是从需要移植的患者身上提取干细胞,在一定的支持条件下允许其生长、增殖、生产为可替换的组织。另一方面,寻找细胞能够互相联结并形成分层结构的合适的支持条件,如基质或支架等非常必要。目前用于烧烫伤治疗的材料有很多种,如胶原,透明质酸、纤维蛋白和聚乳酸及其共聚物。 目的:讨论以新型的生物材料自体血浆为支架对自体成纤维细胞和角质化细胞生长、扩张、增殖的影响。 设计:建立一种真皮再生的方法,将自体成纤维细胞浸于人血浆基质中,排除各种影响样本安全性和排斥反应的问题,应用同样的方法在新的真皮上获取角质化细胞。 时间及地点:实验于2008年在意大利曼多瓦C. Poma医院动物工厂完成。 材料:人角质化细胞和成纤维细胞取自1例58岁乳房切除患者的皮肤碎片。实验得到C. Poma医院独立伦理委员会批准,患者知情同意。 方法:从自体活组织皮肤样本中分离人角质化细胞和成纤维细胞,置于培养瓶中增殖,随后将自体血浆作为皮肤移植形成构造的支架,免疫和免疫组织化学特征显示与正常皮肤相似。 主要观察指标:将血浆样本用甲醛固定,埋入石蜡,苏木精-伊红染色,用显微镜进行细胞计数。所有样本均经免疫组织化学评估。 结果:在血浆基质上获得了多层规则形状的角质化细胞和成纤维细胞,基底膜的形成说明自体血浆是角质化细胞和成纤维细胞的生长、分化、扩展的良好支架,真皮和表皮细胞联结重建皮肤移植与正常皮肤无异。 结论:血浆作为角质化细胞和成纤维细胞分化、扩展的支架表现出良好的性能,同时实验还特别发现成纤维细胞浓缩血浆可以暂时替代皮肤,也是角质化细胞生长的强有力的支架。此外血浆还具有廉价,易于制备等优点。自体角质化细胞和成纤维细胞及自体血浆的应用,可以避免血种类型的免疫排斥反应。这种治疗方法给有慢性缺损并且需要连续移植的患者带来了希望。 doi:10.3969/j.issn.1673-8225.2009.47.001  相似文献   
8.
Abstract:  The identification of tumor-specific proteins located at the plasma membrane is hampered by numerous methodological pitfalls many of which are associated with the post-translational modification of such proteins. Here, we present a new combination of detergent fractionation of cells and of subtractive suppression hybridization (SSH) to gain overexpressed genes coding for membrane-associated or secreted proteins. Fractionation of subcellular components by digitonin allowed sequestering mRNA of the rough Endoplasmatic reticulum and thereby increasing the percentage of sequences coding for membrane-bound proteins. Fractionated mRNAs from the cutaneous T-cell lymphoma (CTCL) cell line HuT78 and from normal peripheral blood monocytes were used for SSH leading to the enrichment of sequences overexpressed in the tumor cells. We identified some 21 overexpressed genes, among them are GPR137B, FAM62A, NOMO1, HSP90, SLIT1, IBP2, CLIF, IRAK and ARC. mRNA expression was tested for selected genes in CTCL cell lines, skin specimens and peripheral blood samples from CTCL patients and healthy donors. Several of the detected sequences are clearly related to cancer, but have not yet been associated with CTCL. qPCR confirmed an enrichment of these mRNAs in the rough endoplasmic reticulum fraction. RT-PCR confirmed the expression of these genes in skin specimens and peripheral blood of CTCL patients. Western blotting verified protein expression of HSP90 and IBP2 in HuT78. GPR137B could be detected by immunohistology in HuT78 and in keratinocytes of dysplastic epidermis, but also in sweat glands of healthy skin. In summary, we developed a new technique, which allows identifying overexpressed genes coding preferentially for membrane-associated proteins.  相似文献   
9.
10.
目的探讨初次献血对红细胞膜Na+-K+-ATP酶活性的影响.方法应用比色法分别检测50例符合献血条件的健康初次献血者献血前后的红细胞膜Na+-K+-ATP酶活性,并对结果进行分析.结果初次献血者献血前后红细胞膜Na+-K+-ATP酶活性分别为3.121±0.441和2.907±0.397 μmol.Pi/107 RBC.h,两者比较无明显差异(P>0.05).结论初次献血对红细胞膜Na+-K+-ATP酶活性无影响,献血不会造成红细胞功能损伤.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号