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   4539篇
  免费   350篇
  国内免费   136篇
  5025篇
  2024年   9篇
  2023年   48篇
  2022年   76篇
  2021年   120篇
  2020年   86篇
  2019年   109篇
  2018年   183篇
  2017年   130篇
  2016年   183篇
  2015年   271篇
  2014年   273篇
  2013年   362篇
  2012年   396篇
  2011年   350篇
  2010年   202篇
  2009年   167篇
  2008年   212篇
  2007年   217篇
  2006年   208篇
  2005年   155篇
  2004年   137篇
  2003年   142篇
  2002年   104篇
  2001年   111篇
  2000年   93篇
  1999年   73篇
  1998年   37篇
  1997年   43篇
  1996年   22篇
  1995年   30篇
  1994年   34篇
  1993年   20篇
  1992年   50篇
  1991年   37篇
  1990年   50篇
  1989年   41篇
  1988年   21篇
  1987年   22篇
  1986年   22篇
  1985年   24篇
  1984年   14篇
  1983年   17篇
  1982年   9篇
  1981年   8篇
  1975年   8篇
  1974年   10篇
  1973年   11篇
  1971年   8篇
  1970年   9篇
  1968年   7篇
排序方式: 共有5025条查询结果,搜索用时 15 毫秒
931.
In October 2012, the Haitian Ministry of Health and the US CDC were notified of 25 recent dengue cases, confirmed by rapid diagnostic tests (RDTs), among non-governmental organization (NGO) workers. We conducted a serosurvey among NGO workers in Léogane and Port-au-Prince to determine the extent of and risk factors for dengue virus infection. Of the total 776 staff from targeted NGOs in Léogane and Port-au-Prince, 173 (22%; 52 expatriates and 121 Haitians) participated. Anti-dengue virus (DENV) IgM antibody was detected in 8 (15%) expatriates and 9 (7%) Haitians, and DENV non-structural protein 1 in one expatriate. Anti-DENV IgG antibody was detected in 162 (94%) participants (79% of expatriates; 100% of Haitians), and confirmed by microneutralization testing as DENV-specific in 17/34 (50%) expatriates and 42/42 (100%) Haitians. Of 254 pupae collected from 68 containers, 65% were Aedes aegypti; 27% were Ae. albopictus. Few NGO workers reported undertaking mosquito-avoidance action. Our findings underscore the risk of dengue in expatriate workers in Haiti and Haitians themselves.  相似文献   
932.
MATERIALS AND METHODS: We examined pretreatment magnetic resonance imaging (MRI) examinations from 32 patients with glioblastoma multiforme (GBM) enrolled in The Cancer Genome Atlas (TCGA). Spatial variations in T1 post-gadolinium and either T2-weighted or fluid attenuated inversion recovery sequences from each tumor MRI study were used to characterize each small region of the tumor by its local contrast enhancement and edema/cellularity (“habitat”). The patient cohort was divided into group 1 (survival < 400 days, n = 16) and group 2 (survival > 400 days, n = 16). RESULTS: Histograms of relative values in each sequence demonstrated that the tumor regions were consistently divided into high and low blood contrast enhancement, each of which could be subdivided into regions of high, low, and intermediate cell density/interstitial edema. Group 1 tumors contained greater volumes of habitats with low contrast enhancement but intermediate and high cell density (not fully necrotic) than group 2. Both leave-one-out and 10-fold cross-validation schemes demonstrated that individual patients could be correctly assigned to the short or long survival group with 81.25% accuracy. CONCLUSION: We demonstrate that novel image analytic techniques can characterize regional habitat variations in GBMs using combinations of MRI sequences. A preliminary study of 32 patients from the TCGA database found that the distribution of MRI-defined habitats varied significantly among the different survival groups. Radiologically defined ecological tumor analysis may provide valuable prognostic and predictive biomarkers in GBM and other tumors.  相似文献   
933.

Introduction

Since persulfate salts are an important cause of occupational asthma (OA), we aimed to study the persistence of respiratory symptoms after a single exposure to ammonium persulfate (AP) in AP-sensitized mice.

Material and Methods

BALB/c mice received dermal applications of AP or dimethylsulfoxide (DMSO) on days 1 and 8. On day 15, they received a single nasal instillation of AP or saline. Airway hyperresponsiveness (AHR) was assessed using methacholine provocation, while pulmonary inflammation was evaluated in bronchoalveolar lavage (BAL), and total serum immunoglobulin E (IgE), IgG1 and IgG2a were measured in blood at 1, 4, 8, 24 hours and 4, 8, 15 days after the single exposure to the causal agent. Histological studies of lungs were assessed.

Results

AP-treated mice showed a sustained increase in AHR, lasting up to 4 days after the challenge. There was a significant increase in the percentage of neutrophils 8 hours after the challenge, which persisted for 24 hours in AP-treated mice. The extent of airway inflammation was also seen in the histological analysis of the lungs from challenged mice. Slight increases in total serum IgE 4 days after the challenge were found, while IgG gradually increased further 4 to 15 days after the AP challenge in AP-sensitized mice.

Conclusions

In AP-sensitized mice, an Ig-independent response is induced after AP challenge. AHR appears immediately, but airway neutrophil inflammation appears later. This response decreases in time; at early stages only respiratory and inflammatory responses decrease, but later on immunological response decreases as well.  相似文献   
934.
935.
Sublingual route has been widely used to deliver small molecules into the bloodstream and to modulate the immune response at different sites. It has been shown to effectively induce humoral and cellular responses at systemic and mucosal sites, namely the lungs and urogenital tract. Sublingual vaccination can promote protection against infections at the lower and upper respiratory tract; it can also promote tolerance to allergens and ameliorate asthma symptoms. Modulation of lung’s immune response by sublingual immunotherapy (SLIT) is safer than direct administration of formulations by intranasal route because it does not require delivery of potentially harmful molecules directly into the airways. In contrast to intranasal delivery, side effects involving brain toxicity or facial paralysis are not promoted by SLIT. The immune mechanisms underlying SLIT remain elusive and its use for the treatment of acute lung infections has not yet been explored. Thus, development of appropriate animal models of SLIT is needed to further explore its potential advantages. This work shows how to perform sublingual administration of therapeutic agents in mice to evaluate their ability to protect against acute pneumococcal pneumonia. Technical aspects of mouse handling during sublingual inoculation, precise identification of sublingual mucosa, draining lymph nodes and isolation of tissues, bronchoalveolar lavage and lungs are illustrated. Protocols for single cell suspension preparation for FACS analysis are described in detail. Other downstream applications for the analysis of the immune response are discussed. Technical aspects of the preparation of Streptococcus pneumoniae inoculum and intranasal challenge of mice are also explained.SLIT is a simple technique that allows screening of candidate molecules to modulate lungs’ immune response. Parameters affecting the success of SLIT are related to molecular size, susceptibility to degradation and stability of highly concentrated formulations.  相似文献   
936.
937.
Centaurea melitensis is a cleistogamous species of Mediterranean distribution, which normally produces a wide range of capitula varying in terms of morphology, size, position in the shoot system and other aspects. For that reason, and particularly in view of the pseudanthic nature of the flower head in Asteraceae, a preliminary study to characterise cleistogamy in this species was considered of interest. Capitular heteromorphism observed inC. melitensis was confirmed by principal component analysis (PCA). The five capitulum types differentiated [initial cleistogamous (iCL), intermediate cleistogamous (xCL), final cleistogamous (fCL), pseudocleistogamous (PCL) and chasmogamous (CH)] fit development patterns specific for both placement on the plant and timing. The balance between cleistogamy and chasmogamy is correlated with the final height of the plant. All these features are consistent with those reported for other cleistogamous species.  相似文献   
938.
罗布泊地区第四纪环境演化   总被引:11,自引:0,他引:11  
新疆罗后干涸湖盆中的K1钻孔揭示,100、2m的沉积剖面共有92个宙积层,划归16同积旋回,包括了早更新世以来的各时期沉积。据划分的15个孢粉组这及古地磁、14^C、岩石地层资料综合分析,早更新世该区曾发育森林-草原植被,早更民末,强烈的构造运动保留我下更充变形,上覆的中更统与下更新统间呈不整合接触。中更新世,荒漠和荒漠草原交替出现,地层中有大量膏质泥岩和石膏。晚更新世以来,在干旱气候的控制之下,  相似文献   
939.
940.
农药鱼藤酮对表达α-突触核蛋白细胞的作用   总被引:3,自引:0,他引:3  
本研究利用农药鱼藤酮作用于神经细胞 ,观察鱼藤酮对神经细胞的损伤作用以及线粒体功能障碍与α- synuclein积聚之间的关系。方法 :本实验选用人神经母细胞瘤细胞株SH-SY5Y ,实验组为α-synuclein GFP基因转染的细胞 ,鱼藤酮处理的转基因细胞和非转基因细胞 ,对照组为未处理的SH-SY5Y细胞。通过RT-PCR检测α-synuclein基因转染细胞的基因表达情况。荧光显微镜观察细胞内α-synuclein GFP表达产物绿色荧光蛋白。MTT法检测各组细胞活性。DCF检测细胞氧应激。HE染色、免疫组化检测α-synuclein在细胞中的状态。电镜观察细胞超微结构的改变。结果 :RT-PCR显示转基因细胞α-synuclein基因的表达。荧光显微镜观察显示细胞浆内可见绿色荧光蛋白 ,绿色荧光分布不均匀 ,可见蛋白积聚。MTT检测结果显示 ,与对照组相比 ,鱼藤酮处理的细胞增殖速度明显减小 (P <0. 01 )。鱼藤酮的浓度为 75nmol/ L、1 0 0nmol/ L时 ,未转基因与转基因的细胞活性相比较 ,前者的细胞活性低于后者 (P <0 .0 5 )。HE染色 ,鱼藤酮处理的转基因细胞胞浆减少、转基因细胞胞浆内也可见自噬体。胞浆内有嗜酸性包涵体样结构。免疫组化可见鱼藤酮处理高表达α-synuclein细胞明显变成梭形并有很长的突起。电镜显示鱼藤酮处理的细胞线粒体肿胀 ,嵴断裂 ,胞浆内形成自噬体。DCF检测转基因细胞内存在明显的氧化应激 ,并随鱼藤酮处理加重。结论 :农药鱼藤酮对多巴胺能神经细胞有明显的损伤作用 ,转基因细胞显示对较高浓度的鱼藤酮损伤有一定的耐受作用。α-synuclein可引起神经细胞的氧化应激并随鱼藤酮处理加重。提示环境因素可能与α-synuclein表达相互作用使多巴胺能神经元氧化应激进行性加重 ,这可能是引起PD的主要原因。  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