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   7313篇
  免费   507篇
  国内免费   272篇
耳鼻咽喉   23篇
儿科学   98篇
妇产科学   59篇
基础医学   461篇
口腔科学   96篇
临床医学   576篇
内科学   1004篇
皮肤病学   69篇
神经病学   175篇
特种医学   149篇
外科学   325篇
综合类   1389篇
预防医学   671篇
眼科学   523篇
药学   935篇
  2篇
中国医学   1382篇
肿瘤学   155篇
  2024年   62篇
  2023年   196篇
  2022年   307篇
  2021年   343篇
  2020年   326篇
  2019年   217篇
  2018年   210篇
  2017年   228篇
  2016年   207篇
  2015年   226篇
  2014年   387篇
  2013年   387篇
  2012年   432篇
  2011年   445篇
  2010年   327篇
  2009年   302篇
  2008年   304篇
  2007年   339篇
  2006年   265篇
  2005年   241篇
  2004年   193篇
  2003年   193篇
  2002年   145篇
  2001年   141篇
  2000年   122篇
  1999年   105篇
  1998年   65篇
  1997年   67篇
  1996年   61篇
  1995年   92篇
  1994年   95篇
  1993年   43篇
  1992年   41篇
  1991年   38篇
  1990年   36篇
  1989年   43篇
  1985年   55篇
  1984年   77篇
  1983年   43篇
  1982年   41篇
  1981年   34篇
  1980年   53篇
  1979年   28篇
  1978年   29篇
  1947年   25篇
  1946年   28篇
  1943年   29篇
  1942年   26篇
  1938年   30篇
  1935年   26篇
排序方式: 共有8092条查询结果,搜索用时 31 毫秒
71.

Background

Myositis is a heterogeneous group of muscular auto-immune diseases with clinical and pathological criteria that allow the classification of patients into different sub-groups. Inclusion body myositis is the most frequent myositis above fifty years of age. Diagnosing inclusion body myositis requires expertise and is challenging. Little is known concerning the pathogenic mechanisms of this disease in which conventional suppressive-immune therapies are inefficacious.

Objectives

Our aim was to deepen our understanding of the immune mechanisms involved in inclusion body myositis and identify specific biomarkers.

Methods

Using a panel of thirty-six markers and mass cytometry, we performed deep immune profiling of peripheral blood cells from inclusion body myositis patients and healthy donors, divided into two cohorts: test and validation cohorts. Potential biomarkers were compared to myositis controls (anti-Jo1-, anti-3-hydroxyl-3-methylglutaryl CoA reductase-, and anti-signal recognition particle-positive patients).

Results

Unsupervised analyses revealed substantial changes only within CD8+ cells. We observed an increase in the frequency of CD8+ cells that expressed high levels of T-bet, and containing mainly both effector and terminally differentiated memory cells. The senescent marker CD57 was overexpressed in CD8+T-bet+ cells of inclusion body myositis patients. As expected, senescent CD8+T-bet+ CD57+ cells of both patients and healthy donors were CD28nullCD27nullCD127null. Surprisingly, non-senescent CD8+T-bet+ CD57- cells in inclusion body myositis patients expressed lower levels of CD28, CD27, and CD127, and expressed higher levels of CD38 and HLA-DR compared to healthy donors. Using classification and regression trees alongside receiver operating characteristics curves, we identified and validated a frequency of CD8+T-bet+ cells >51.5% as a diagnostic biomarker specific to inclusion body myositis, compared to myositis control patients, with a sensitivity of 94.4%, a specificity of 88.5%, and an area under the curve of 0.97.

Conclusion

Using a panel of thirty-six markers by mass cytometry, we identify an activated cell population (CD8+T-bet+ CD57- CD28lowCD27lowCD127low CD38+ HLA-DR+) which could play a role in the physiopathology of inclusion body myositis, and identify CD8+T-bet+ cells as a predominant biomarker of this disease.  相似文献   
72.
目的 研究5-羟色胺受体102T/C多态性是否与Tourette综合征(TS)相关联,方法对157个核心家系样本采用病例-对照关联分析,传递不平衡检验方法,聚合酶链反应及RFLP等技术,根据TS与强迫症(obsessive compulsive disorder,OCD)的同病现象,将TS划分亚组进行与5-羟色胺受体102T/C多态性的关联分析。结果 合并OCD的TS与该位点的基因型102C/C(X2=8.38,P=0.004)及等位基因102C/(X2=4.84,P=0.028)存在关联,进一步采用传递不平衡分析,发现合并(美国精神疾病诊断和统计手册IV》论断标准的OCD的TS与该位点存在关联或连锁不平衡(X2=5.12,,P=0.02),而在TS总体样本及单纯TS样本中未发现与该位点的关联,结论 5-羟色胺受体102T/C多态性与中国人群合并OCD的TS存在关联,合并OCD的TS可能是TS中相对独立的一个亚型。  相似文献   
73.
目的:探讨昏迷病人的脑电图(EEG)诊断对估计预后的价值。方法:回顾性分析96例昏迷病人床边EEG。结果:EEG表现为平坦波或暴发抑制波异常预后不良,均死亡,EEG以α波为主,混有θ,β波,预后良好;而为δ,θ,β波,其预后难确定,还需随访。结论;昏迷病人进行床边EEG检查,可以检测脑功能,而且对最终预后作出较为肯定的评价。  相似文献   
74.
以无毒氧化葡萄糖醛作交联剂 ,采用溶液共混交联法制备壳聚糖改性丝素合金膜。用 FTIR、DSC表征其结构 ,测定其等电点、力学性能、不同 p H条件下的溶胀率和对模型药物 5 - Fu的渗透性。结果表明 :改性丝素合金膜中丝素和壳聚糖分子间存在着强烈的氢键相互作用及良好的相容性。改性膜的等电点对应的 p H值是 5 .35 ,而丝素膜的等电点是 4 .5。改性膜的力学性能优于单组分膜 ,当壳聚糖含量为 4 0 %~ 6 0 %时 ,具有最大的抗张强度和拉伸率 ,分别为 71.4~ 72 .7MPa和 2 .96~ 3.82 %。改性丝素合金膜对 5 - Fu的渗透量与壳聚糖的含量和时间成正相关关系 ,渗透系数随 p H值增大 (5→ 9)先逐渐减小然后略有增大 ,在 p H=7时最小。  相似文献   
75.
Alleles at the brown locus ofDrosophila melanogaster combined with homozygous scarlet provide a useful model to demonstrate minority advantage of males in mating. Heterozygotes with orange (O) eyes equal in numbers to homozygotes with red (R) eyes (1010 in both sexes) displayed no bias favoring either eye color, but each eye color was favored when males occurred in a minority ratio (218). In direct observation of single females with equal numbers of males (33) as controls,O males courted less and more slowly thanR males, but females mated with either type without bias. When unequal (41), the minority males were successful at more than twice the frequency expected. Whether successful or not, the minority males did not change their level of courtship, and thus cannot be said to compensate for their frequency in any way. The time between first courtship and mating was less for the minority males than for the majority males. We discard the hypothesis that the minority male will be accepted immediately or ahead of a majority male, because the opposite tended to occur: that if a minority male courted first he was less likely to be successful than if he waited until the majority courted. Our results then are in conformity with the hypothesis that a female samples males and their courtship cues, thus becoming habituated to the majority of the first courting male, but she accepts a male with a cue different from that which she originally detected but avoided. That male is most often the minority.This research was supported in part by National Science Foundation Grants GB-34206 to August 31, 1974, and BMS 72-02110 after that date.  相似文献   
76.
Macrophages are known to release reactive oxygen species (O2?, 1O2, H2O2, OH·) in response to various membrane stimuliHowever, our studies show that phagocytic stimulation of macrophages is not necessarily accompanied by a stimulation of the oxidative burstWhereas IgG-opsonized erythrocytes were capable to induce phagocytosis and a chemiluminescence response, both being dependent on the number of IgG bound per erythrocyte, C3b-bearing erythrocytes were well ingested but failed to induce any chemiluminescence reactionFurthermore, stimulation of macrophages, via the Fc-receptors, seems to alter their functional state in regard to the activation of a receptor, which enables them to recognize membrane lesions on the target erythrocyteThe presence of IgG and membrane lesions, e.gthe C5b-9-complex of complement, induced a marked increase in chemiluminescence compared with stimulation by IgG-bearing particles aloneThe augmented response of macrophages was at least in part due to an additional release of H2O2, which was not liberated in response to IgG-bearing erythrocytesThis «Alesion recognizing receptor» in the macrophage membrane could not be activated by stimulation of C3b-receptors, indicating its functional linkage to the Fc-receptors.  相似文献   
77.
Pseudoachondroplasia (PSACH) and some forms of multiple epiphyseal dysplasia (MED) result from mutations in the gene encoding cartilage oligomeric matrix protein (COMP). COMP is a large pentameric glycoprotein found predominantly in the extracellular matrix of cartilage, tendon, and ligament. As a modular protein, it is composed of a coiled-coil domain, four type II (T2) repeats, eight type III (T3) repeats, and a large globular C-terminal domain (CTD). The majority (>85%) of COMP mutations causing PSACH or MED are found in the exons encoding the T3 repeats, and the disease mechanism has been characterised in detail. Much less is known about disease-causing mutations in the CTD; in 10 years only seven mutations have been identified. In this study, we describe eight novel and two recurrent mutations that we have recently identified in patients with PSACH or MED. Interestingly, these mutations result in a spectrum of disease, ranging from mild MED to severe PSACH. Mapping of all known COMP CTD mutations on a three-dimensional model of the C-terminal domain shows that the CTD mutations cluster in two distinct regions. These regions are probably important in stabilising the T3-CTD structure and mediating intra- or intermolecular interactions.  相似文献   
78.
基于扩展Infomax ICA的ERP少次提取方法研究   总被引:1,自引:0,他引:1  
事件相关电位(event related potential,ERP)提取是脑电研究的重点之一,目前临床上主要通过相干平均的方法来获取.由于脑电的非平稳性,使其需要大量重复刺激才能获得,对于受试者极不方便,也不利于ERP的实时检测.本文以反映大脑稀少认知事件的相关电位P300为例,采用扩展Infomax(extended informationmaximization)独立分量分析(independent component analysis,ICA)算法,先滤除眼动、工频干扰,再重构脑电数据,最后经少次叠加即可得到与通常需多次相干平均结果相近的比较满意的P300波形.说明ICA算法在ERP的峰值和潜伏期模式识别上具有较为明显的效果,具有潜在的临床工程应用价值.  相似文献   
79.
In one patient, an epithelioid cell nevus of the conjunctiva contained numerous large, unpigmented, mononucleated, binucleated, and multinucleated benign-appearing nevus cells with abundant cytoplasm and frequent intranuclear vacuoles. Despite their overall size, the cells manifested a low nuclear-cytoplasmic ratio. After a partial excision of the lesion, the remainder spontaneously regressed during a two-year period. Another patient's lesion was dominated by a proliferation of spindle nevus cells developing in a long-standing epibulbar nevus. The spindle cells were moderately pigmented, frequently located within walls of epithelial inclusion cysts, and had benign cytologic features. Finally, in a third patient with the cutaneous B-K mole syndrome, a dysplastic conjunctival nevus developed that featured intraepithelial, atypical melanocytic proliferation with superficial colonization of the substantia propria. This portion coexisted with a deeper, preexistent lesion in the substantia propria that was comprised of orderly nests of unpigmented cuboidal nevus cells surrounded by pigmented, spindle-shaped blue nevus cells--a so-called "mixed nevus."  相似文献   
80.
A study to ascertain suitable conditions for handling biological samples from patients, treated with the antibiotic mitomycin C (MMC), with the objective of improving the accuracy and reliability of the determination is described. Situations frequently occurring in medical practice are simulated to optimize procedures for reliable and reproducible sampling, sample treatment and determination of MMC. Continuation of drug partitioning in whole blood after sampling can be prevented by immediate cooling in ice before the separation of plasma from cells. The adjustment of the pH of urine samples is shown to be particularly important since a low urinary pH causes decomposition of MMC; moreover, it may decrease extraction recovery. Furthermore, long-term exposure of samples to daylight induces drug decomposition. Frozen storage of plasma and urine samples for periods greater than 3 weeks is to be avoided as this results in a considerable drop in MMC concentration. Repeated cycles of freezing and thawing are shown to have no effect upon the analytical results (6 cycles tested). The analysis of extracts of biological samples may take place up to at least 24 h after their preparation without measurable loss of analyte.  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