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   2523篇
  免费   220篇
  国内免费   208篇
  2951篇
  2024年   4篇
  2023年   27篇
  2022年   88篇
  2021年   121篇
  2020年   85篇
  2019年   94篇
  2018年   107篇
  2017年   76篇
  2016年   132篇
  2015年   174篇
  2014年   164篇
  2013年   192篇
  2012年   238篇
  2011年   215篇
  2010年   119篇
  2009年   86篇
  2008年   129篇
  2007年   117篇
  2006年   95篇
  2005年   93篇
  2004年   79篇
  2003年   66篇
  2002年   61篇
  2001年   50篇
  2000年   41篇
  1999年   44篇
  1998年   31篇
  1997年   33篇
  1996年   30篇
  1995年   26篇
  1994年   16篇
  1993年   13篇
  1992年   16篇
  1991年   10篇
  1990年   15篇
  1989年   7篇
  1988年   7篇
  1987年   13篇
  1986年   6篇
  1985年   8篇
  1984年   4篇
  1983年   3篇
  1978年   1篇
  1977年   2篇
  1975年   3篇
  1974年   2篇
  1971年   2篇
  1969年   1篇
  1968年   1篇
  1965年   1篇
排序方式: 共有2951条查询结果,搜索用时 15 毫秒
901.

Objectives

Acute meningitis and encephalitis (AME) are common diseases with the main pathogens being viruses and bacteria. As specific treatments are different, it is important to develop clinical prediction rules to distinguish aseptic from bacterial or fungal infection. In this study we evaluated the incidence rates, seasonal variety and the main etiologic agents of AME, and identified factors that could be used to predict the etiologic agents.

Methods

A population-based AME syndrome surveillance system was set up in Guigang City, Guangxi, involving 12 hospitals serving the study communities. All patients meeting the case definition were investigated. Blood and/or cerebrospinal fluid were tested for bacterial pathogens using culture or RT-PCR and serological tests for viruses using enzyme-linked immunosorbent assays. Laboratory testing variables were grouped using factor analysis. Multinomial logistic regression was used to predict the etiology of AME.

Results

From May 2007 to June 2012, the annual incidence rate of AME syndrome, and disease specifically caused by Japanese encephalitis (JE), other viruses, bacteria and fungi were 12.55, 0.58, 4.57, 0.45 and 0.14 per 100,000 population, respectively. The top three identified viral etiologic agents were enterovirus, mumps virus, and JE virus, and for bacteria/fungi were Streptococcus sp., Cryptococcus neoformans and Staphylococcus sp. The incidence of JE and other viruses affected younger populations and peaked from April to August. Alteration of consciousness and leukocytosis were more likely to be caused by JE, bacteria and fungi whereas CSF inflammation was associated with bacterial/fungal infection.

Conclusions

With limited predictive validity of symptoms and signs and routine laboratory tests, specific tests for JE virus, mumps virus and enteroviruses are required to evaluate the immunization impact and plan for further intervention. CSF bacterial culture cannot be omitted in guiding clinical decisions regarding patient treatment.  相似文献   
902.

Purpose

This study was aimed to identify the expression pattern of vascular endothelial growth factor (VEGF) in non-small cell lung cancer (NSCLC) and to explore its potential correlation with the progression of NSCLC.

Methods

Gene expression profile GSE39345 was downloaded from the Gene Expression Omnibus database. Twenty healthy controls and 32 NSCLC samples before chemotherapy were analyzed to identify the differentially expressed genes (DEGs). Then pathway enrichment analysis of the DEGs was performed and protein-protein interaction networks were constructed. Particularly, VEGF genes and the VEGF signaling pathway were analyzed. The sub-network was constructed followed by functional enrichment analysis.

Results

Total 1666 up-regulated and 1542 down-regulated DEGs were identified. The down-regulated DEGs were mainly enriched in the pathways associated with cancer. VEGFA and VEGFB were found to be the initiating factor of VEGF signaling pathway. In addition, in the epidermal growth factor receptor (EGFR), VEGFA and VEGFB associated sub-network, kinase insert domain receptor (KDR), fibronectin 1 (FN1), transforming growth factor beta induced (TGFBI) and proliferating cell nuclear antigen (PCNA) were found to interact with at least two of the three hub genes. The DEGs in this sub-network were mainly enriched in Gene Ontology terms related to cell proliferation.

Conclusion

EGFR, KDR, FN1, TGFBI and PCNA may interact with VEGFA to play important roles in NSCLC tumorigenesis. These genes and corresponding proteins may have the potential to be used as the targets for either diagnosis or treatment of patients with NSCLC.  相似文献   
903.
Increased incidence of hand, foot and mouth disease (HFMD) has been recognized as a critical challenge to communicable disease control and public health response. This study aimed to quantify the association between climate variation and notified cases of HFMD in selected cities of Shanxi Province, and to provide evidence for disease control and prevention. Meteorological variables and HFMD cases data in 4 major cities (Datong, Taiyuan, Changzhi and Yuncheng) of Shanxi province, China, were obtained from the China Meteorology Administration and China CDC respectively over the period 1 January 2009 to 31 December 2013. Correlations analyses and Seasonal Autoregressive Integrated Moving Average (SARIMA) models were used to identify and quantify the relationship between the meteorological variables and HFMD. HFMD incidence varied seasonally with the majority of cases in the 4 cities occurring from May to July. Temperatures could play important roles in the incidence of HFMD in these regions. The SARIMA models indicate that a 1° C rise in average, maximum and minimum temperatures may lead to a similar relative increase in the number of cases in the 4 cities. The lag times for the effects of temperatures were identified in Taiyuan, Changzhi and Yuncheng. The numbers of cases were positively associated with average and minimum temperatures at a lag of 1 week in Taiyuan, Changzhi and Yuncheng, and with maximum temperature at a lag of 2 weeks in Yuncheng. Positive association between the temperature and HFMD has been identified from the 4 cities in Shanxi Province, although the role of weather variables on the transmission of HFMD varied in the 4 cities. Relevant prevention measures and public health action are required to reduce future risks of climate change with consideration of local climatic conditions.  相似文献   
904.
The current event-related potential study investigated the modulation effects of different emotion regulation strategies on electrocortical responses. When watching negative or neutral pictures, participants were instructed to perform three tasks: cognitive reappraisal, expressive suppression and passive viewing. We found that negative pictures elicited a larger late positive potential (LPP) than neutral pictures. Moreover, processes involved in strategy also had an effect on LPP amplitude, which was indicated by a larger LPP in reappraisal compared with suppression and viewing tasks when neutral pictures were presented. After the influence of processes on LPP was excluded, results showed that reappraisal effectively decreased the emotion-enhanced LPP than suppression and viewing. The difference in regulatory effect may be determined by the underlying processing mechanism. A larger frontal-central component, N2, was observed in suppression than reappraisal and viewing, which suggested that it involved the processes focusing on behavioral response. While the larger LPP found in reappraisal implicated that it recruited cognitive processes focusing on the picture meaning.  相似文献   
905.

Background

Ki67 labeling index (LI) is used as a predictive marker and is associated with prognosis in breast cancer. However, standardised methodologies for measurement are lacking which has limited its application in clinical practice. In this study, we evaluated the interobserver concordance of visual assessment of Ki67 LI in breast cancer.

Methods

Ki67- immunostained slides of 160 cases of primary invasive breast cancer were visual assessed by five breast pathologists with two different methods to choose the scoring fields: (1) hot-spot score, (2) average score. Proportions of positive invasive tumor cells at 10 % intervals were scored. The intra-class correlation coefficient (ICC) was used to assess the interobserver reproducibility.

Results

(1) A perfect concordance of Ki67 LI was demonstrated according to both score methods (P<0.0001). Average score method (ICC, 0.904) demonstrated a better correlation than hot-spot score method (ICC, 0.894). (2) By respective means according to two score methods, all cases were classified into three groups (≤10%, 11%-30% and >30% Ki-67 LI). The concordance was relatively low in intermediate Ki67 LI group compared with low and high Ki67 LI groups. (3) All cases were classified into three groups by paired-difference (d) between means of hot-spot score and average score (d<5, 5≤d<10, d≥10). The consistency was observed to decrease with increasing paired-difference according to both methods.

Conclusions

Visual assessment of Ki67 LI at 10 % intervals is a candidate for a standard method in breast cancer clinical practice. Average score and hot-spot score of visual assessment both demonstrated a perfect concordance, and an overall average assessment across the whole section including hot spots may be a better method. Interobserver concordance of intermediate Ki67 LI in which most cutoffs are located for making clinical decisions was relatively low.  相似文献   
906.
The family Orchidaceae is not only one of the most diverse families of flowering plants, but also one of the most endangered plant taxa. Therefore, understanding how its species richness varies along geographical and environmental gradients is essential for conservation efforts. However, such knowledge is rarely available, especially on a large scale. We used a database extracted from herbarium records to investigate the relationships between orchid species richness and elevation, and to examine how elevational diversity in Yunnan Province, China, might be explained by mid-domain effect (MDE), species–area relationship (SAR), water–energy dynamics (WED), Rapoport’s Rule, and climatic variables. This particular location was selected because it is one of the primary centers of distribution for orchids. We recorded 691 species that span 127 genera and account for 88.59% of all confirmed orchid species in Yunnan. Species richness, estimated at 200-m intervals along a slope, was closely correlated with elevation, peaking at 1395 to 1723 m. The elevational pattern of orchid richness was considerably shaped by MDE, SAR, WED, and climate. Among those four predictors, climate was the strongest while MDE was the weakest for predicting the elevational pattern of orchid richness. Species richness showed parabolic responses to mean annual temperature (MAT) and mean annual precipitation (MAP), with maximum richness values recorded at 13.7 to 17.7°C for MAT and 1237 to 1414 mm for MAP. Rapoport’s Rule also helped to explain the elevational pattern of species richness in Yunnan, but those influences were not entirely uniform across all methods. These results suggested that the elevational pattern of orchid species richness in Yunnan is collectively shaped by several mechanisms related to geometric constraints, size of the land area, and environments. Because of the dominant role of climate in determining orchid richness, our findings may contribute to a better understanding of the potential effects of climate change on orchid diversity, and the development of conservation strategies for orchids.  相似文献   
907.
Sucrose synthase (SuSy) is considered the first key enzyme for secondary growth because it is a highly regulated cytosolic enzyme that catalyzes the reversible conversion of sucrose and UDP into UDP-glucose and fructose. Although SuSy enzymes preferentially functions in the direction of sucrose cleavage at most cellular condition, they also catalyze the synthetic reaction. We isolated a gene that encodes a SuSy from Populus simonii×Populus nigra and named it PsnSuSy2 because it shares high similarity to SuSy2 in Populus trichocarpa. RT-PCR revealed that PsnSuSy2 was highly expressed in xylem, but lowly expressed in young leaves. To characterize its functions in secondary growth, multiple tobacco overexpression transgenic lines of PnsSuSy2 were generated via Agrobacterium-mediated transformation. The PsnSuSy2 expression levels and altered wood properties in stem segments from the different transgenic lines were carefully characterized. The results demonstrated that the levels of PsnSuSy2 enzyme activity, chlorophyll content, total soluble sugars, fructose and glucose increased significantly, while the sucrose level decreased significantly. Consequently, the cellulose content and fiber length increased, whereas the lignin content decreased, suggesting that PsnSuSy2 plays a significant role in cleaving sucrose into UDP-glucose and fructose to facilitate cellulose biosynthesis and that promotion of cellulose biosynthesis suppresses lignin biosynthesis. Additionally, the noticeable increase in the lodging resistance in transgenic tobacco stem suggested that the cell wall characteristics were altered by PsnSuSy2 overexpression. Scanning electron microscopy was performed to study the cell wall morphology of stem, and surprisingly, we found that the secondary cell wall was significantly thicker in transgenic tobacco. However, the thickened secondary cell wall did not negatively affect the height of the plants because the PsnSuSy2- overexpressing lines grew taller than the wildtype plants. This systematic analysis demonstrated that PsnSuSy2 plays an important role in cleaving sucrose coupled with cellulose biosynthesis in wood tissue.  相似文献   
908.

Background

Studies on cognition in multiple system atrophy (MSA) patients are limited.

Methods

A total of 110 MSA patients were evaluated using Addenbrooke''s Cognitive Examination-Revised (ACE-R), Frontal Assessment Battery (FAB), Frontal Behavioral Inventory (FBI), and Unified MSA Rating Scale (UMSARS) tests. Fifty-five age-, sex-, education- and domicile-matched healthy controls were recruited to perform the FAB and ACE-R scales.

Results

Approximately 32.7% of the patients had global cognitive deficits with the most impaired domain being verbal fluency and visuospatial ability (26.4%), followed by memory (24.5%), language (20%) and orientation/attention (20%) based on a cut-off score of ACE-R ≤ 70. A total of 41.6% of the patients had frontal lobe dysfunction, with inhibitory control (60.9%) as the most impaired domain based on a cut-off score of FAB ≤14. Most patients (57.2%) showed moderate frontal behavior changes (FBI score 4–15), with incontinence (64.5%) as the most impaired domain. The binary logistic regression model revealed that an education level < 9 years (OR:13.312, 95% CI:2.931–60.469, P = 0.001) and UMSARS ≥ 40 (OR: 2.444, 95%CI: 1.002–5.962, P< 0.049) were potential determinants of abnormal ACE-R, while MSA-C (OR: 4.326, 95%CI: 1.631–11.477, P = 0.003), an education level < 9 years (OR:2.809 95% CI:1.060–7.444, P = 0.038) and UMSARS ≥ 40 (OR:5.396, 95%CI: 2.103–13.846, P < 0.0001) were potential determinants of abnormal FAB.

Conclusions

Cognitive impairment is common in Chinese MSA patients. MSA-C patients with low education levels and severe motor symptoms are likely to experience frontal lobe dysfunction, while MSA patients with low education levels and severe motor symptoms are likely to experience global cognitive deficits. These findings strongly suggest that cognitive impairment should not be an exclusion criterion for the diagnosis of MSA.  相似文献   
909.
The determination of hormone‐binding sites in plants is essential in understanding the mechanisms behind hormone function. Salicylic acid (SA) is an important plant hormone that regulates responses to biotic and abiotic stresses. In order to label SA‐binding sites in plant tissues, a quantum dots (QDs) probe functionalized with a SA moiety was successfully synthesized by coupling CdSe QDs capped with 3‐mercaptopropionic acid (MPA) to 4‐amino‐2‐hydroxybenzoic acid (PAS), using 1‐ethyl‐3‐(3‐dimethyllaminopropyl) carbodiimide (EDC) as the coupling agent. The probe was then characterized by dynamic light scattering and transmission electron microscopy, as well as UV/vis and fluorescence spectrophotometry. The results confirmed the successful conjugation of PAS to CdSe QDs and revealed that the conjugates maintained the properties of the original QDs, with small core diameters and adequate dispersal in solution. The PAS–CdSe QDs were used to detect SA‐binding sites in mung bean and Arabidopsis thaliana seedlings in vitro and in vivo. The PAS–CdSe QDs were effectively transported into plant tissues and specifically bound to SA receptors in vivo. In addition, the effects of the PAS–CdSe QDs on cytosolic Ca2+ levels in the tips of A. thaliana seedlings were investigated. Both SA and PAS–CdSe QDs had similar effects on the trend in cytosolic‐free Ca2+ concentrations, suggesting that the PAS–CdSe QDs maintained the bioactivity of SA. To summarize, PAS–CdSe QDs have high potential as a fluorescent probe for the in vitro/in vivo labeling and imaging of SA receptors in plants. Copyright © 2014 John Wiley & Sons, Ltd.  相似文献   
910.
The PctC chemoreceptor of Pseudomonas aeruginosa mediates chemotaxis with high specificity to gamma‐aminobutyric acid (GABA). This compound is present everywhere in nature and has multiple functions, including being a human neurotransmitter or plant signaling compound. Because P. aeruginosa is ubiquitously distributed in nature and able to infect and colonize different hosts, the physiological relevance of GABA taxis is unclear, but it has been suggested that bacterial attraction to neurotransmitters may enhance virulence. We report the identification of McpG as a specific GABA chemoreceptor in non‐pathogenic Pseudomonas putida KT2440. As with PctC, GABA was found to bind McpG tightly. The analysis of chimeras comprising the PctC and McpG ligand‐binding domains fused to the Tar signaling domain showed very high GABA sensitivities. We also show that PctC inactivation does not alter virulence in Caenorhabditis elegans. Significant amounts of GABA were detected in tomato root exudates, and deletion of mcpG reduced root colonization that requires chemotaxis through agar. The C. elegans data and the detection of a GABA receptor in non‐pathogenic species indicate that GABA taxis may not be related to virulence in animal systems but may be of importance in the context of colonization and infection of plant roots by soil‐dwelling pseudomonads.  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