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   1151篇
  免费   73篇
  2023年   5篇
  2022年   4篇
  2021年   13篇
  2020年   3篇
  2019年   3篇
  2018年   9篇
  2017年   10篇
  2016年   26篇
  2015年   38篇
  2014年   60篇
  2013年   62篇
  2012年   88篇
  2011年   117篇
  2010年   98篇
  2009年   59篇
  2008年   59篇
  2007年   61篇
  2006年   68篇
  2005年   56篇
  2004年   44篇
  2003年   41篇
  2002年   45篇
  2001年   9篇
  2000年   12篇
  1999年   20篇
  1998年   19篇
  1997年   9篇
  1996年   13篇
  1995年   18篇
  1994年   18篇
  1993年   8篇
  1992年   8篇
  1991年   8篇
  1990年   8篇
  1989年   7篇
  1988年   11篇
  1987年   4篇
  1986年   6篇
  1985年   8篇
  1984年   12篇
  1983年   8篇
  1982年   11篇
  1981年   10篇
  1980年   5篇
  1978年   3篇
  1977年   4篇
  1976年   3篇
  1975年   2篇
  1974年   3篇
  1969年   2篇
排序方式: 共有1224条查询结果,搜索用时 281 毫秒
991.
Frateuria aurantia (ex Kondô and Ameyama 1958) Swings et al. 1980 is a member of the bispecific genus Frateuria in the family Xanthomonadaceae, which is already heavily targeted for non-type strain genome sequencing. Strain Kondô 67T was initially (1958) identified as a member of ‘Acetobacter aurantius’, a name that was not considered for the approved list. Kondô 67T was therefore later designated as the type strain of the newly proposed acetogenic species Frateuria aurantia. The strain is of interest because of its triterpenoids (hopane family). F. aurantia Kondô 67T is the first member of the genus Frateura whose genome sequence has been deciphered, and here we describe the features of this organism, together with the complete genome sequence and annotation. The 3,603,458-bp long chromosome with its 3,200 protein-coding and 88 RNA genes is a part of the Genomic Encyclopedia of Bacteria and Archaea project.  相似文献   
992.

Background

amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that leads to death within a few years after diagnosis. Malnutrition and weight loss are frequent and are indexes of poor prognosis. Total body fat and fat distribution have not been studied in ALS patients.

Objectives

Our aim was to describe adipose tissue content and distribution in ALS patients.

Design

We performed a cross-sectional study in a group of ALS patients (n = 62, mean disease duration 22 months) along with age and gender matched healthy controls (n = 62) using a MRI-based method to study quantitatively the fat distribution.

Results

Total body fat of ALS patients was not changed as compared with controls. However, ALS patients displayed increased visceral fat and an increased ratio of visceral to subcutaneous fat. Visceral fat was not correlated with clinical severity as judged using the ALS functional rating scale (ALS-FRS-R), while subcutaneous fat in ALS patients correlated positively with ALS-FRS-R and disease progression. Multiple regression analysis showed that gender and ALS-FRS-R, but not site of onset, were significant predictors of total and subcutaneous fat. Increased subcutaneous fat predicted survival in male patients but not in female patients (p<0.05).

Conclusions

Fat distribution is altered in ALS patients, with increased visceral fat as compared with healthy controls. Subcutaneous fat content is a predictor of survival of ALS patients.  相似文献   
993.
Riparian savanna habitats grazed by hippopotamus or livestock experience seasonal ecological stresses through the depletion of herbaceous vegetation, and are often points of contacts and conflicts between herbivores, humans and their livestock. We investigated how hippopotamus and livestock grazing influence vegetation structure and cover and facilitate other wild herbivores in the Mara region of Kenya. We used 5 km-long transects, each with 13 plots measuring 10 × 10 m2, and which radiate from rivers in the Masai Mara National Reserve and adjoining community pastoral ranches. For each plot, we measured the height and visually estimated the percent cover of grasses, forbs, shrubs and bare ground, herbivore abundance and species richness. Our results showed that grass height was shortest closest to rivers in both landscapes, increased with increasing distance from rivers in the reserve, but was uniformly short in the pastoral ranches. Shifting mosaics of short grass lawns interspersed with patches of medium to tall grasses occurred within 2.5 km of the rivers in the reserve in areas grazed habitually by hippos. Hence, hippo grazing enhanced the structural heterogeneity of vegetation but livestock grazing had a homogenizing effect in the pastoral ranches. The distribution of biomass and the species richness of other ungulates with distance from rivers followed a quadratic pattern in the reserve, suggesting that hippopotamus grazing attracted more herbivores to the vegetation patches at intermediate distances from rivers in the reserve. However, the distribution of biomass and the species richness of other ungulates followed a linear pattern in the pastoral ranches, implying that herbivores avoided areas grazed heavily by livestock in the pastoral ranches, especially near rivers.  相似文献   
994.

Introduction

Fast in-vivo high resolution diffusion tensor imaging (DTI) of the mouse brain has recently been shown to enable cohort studies by the combination of appropriate pulse sequences and cryogenically cooled resonators (CCR). The objective of this study was to apply this DTI approach at the group level to β-amyloid precursor protein (APP) transgenic mice.

Methods

Twelve mice (5 wild type, 7 APP transgenic tg2576) underwent DTI examination at 1562×250 µm3 spatial resolution with a CCR at ultrahigh field (11.7 T). Diffusion images were acquired along 30 gradient directions plus 5 references without diffusion encoding with a total acquisition time of 35 minutes. Fractional anisotropy (FA) maps were statistically compared by whole brain-based spatial statistics (WBSS) at the group level vs. wild type controls.

Results

FA-map comparison showed characteristic regional patterns of differences between the groups with localizations associated with Alzheimer’s disease in humans, such as the hippocampus, the entorhinal cortex, and the caudoputamen.

Conclusion

In this proof-of-principle study, regions associated with amyloid-β deposition could be identified by WBSS of FA maps in APP transgenic mice vs. wild type mice. Thus, DTI in the mouse brain acquired at 11.7 T by use of a CCR was demonstrated to be feasible for cohort studies.  相似文献   
995.

Background

Acute exacerbations of chronic bronchitis (AECB), including chronic obstructive pulmonary disease (AECOPD), represent a substantial patient burden. Few data exist on outpatient antibiotic management for AECB/AECOPD in Eastern/South Eastern Europe, in particular on the use of moxifloxacin (Avelox®), although moxifloxacin is widely approved in this region based on evidence from international clinical studies.

Methods

AVANTI (AVelox® in Acute Exacerbations of chroNic bronchiTIs) was a prospective, observational study conducted in eight Eastern European countries in patients?>?35 years with AECB/AECOPD to whom moxifloxacin was prescribed. In addition to safety and efficacy outcomes, data on risk factors and the impact of exacerbation on daily life were collected.

Results

In the efficacy population (N?=?2536), chronic bronchitis had been prevalent for?>?10 years in 31.4% of patients and 66.0% of patients had concomitant COPD. Almost half the patients had never smoked, in contrast to data from Western Europe and the USA, where only one-quarter of COPD patients are non-smokers. The mean number of exacerbations in the last 12 months was 2.7 and 26.3% of patients had been hospitalized at least once for exacerbation. Physician compliance with the recommended moxifloxacin dose (400 mg once daily) was 99.6%. The mean duration of moxifloxacin therapy for the current exacerbation (Anthonisen type I or II in 83.1%; predominantly type I) was 6.4?±?1.9 days. Symptom improvement was reported after a mean of 3.4?±?1.4 days. After 5 days, 93.2% of patients reported improvement and, in total, 93.5% of patients were symptom-free after 10 days. In the safety population (N?=?2672), 57 (2.3%) patients had treatment-emergent adverse events (TEAEs) and 4 (0.15%) had serious TEAEs; no deaths occurred. These results are in line with the known safety profile of moxifloxacin.

Conclusions

A significant number of patients in this observational study had risk factors for poor outcome, justifying use of moxifloxacin. The safety profile of moxifloxacin and its value as an antibiotic treatment were confirmed. Physicians complied with the recommended 400 mg once-daily dose in a large proportion of patients, confirming the advantages of this simple dosing regimen.

Trial registration

ClinicalTrials.gov identifier: NCT00846911  相似文献   
996.
The rare apothecial, cupulate fungus Geopora pellita (Pyronemataceae) is characterized by a uniquely bright yellow-orange excipulum. We here re-examine its affiliations by use of morphological, molecular phylogenetic and ultrastructural analyses. G. pellita appears as phylogenetically rather isolated, being the sister group of a clade comprising Phaeangium, Picoa, the majority of the Tricharina species, and the remaining Geopora species. Based on its phylogenetic position and its unique combination of morphological characters, we assign G. pellita to Hoffmannoscypha, gen. nov., as H. pellita, comb. nov. As in a previous study, analyses of both large subunit (LSU) and internal transcribed spacer (ITS) ribosomal DNA suggest that the remaining genus Geopora is paraphyletic, with the hypogeous, ptychothecial type species more closely related to Picoa and Phaeangium than to the greyish-brownish cupulate and apothecial Geopora spp., indicating that the latter should be reassigned to the genus Sepultaria. The current study also shows that ITS confirm LSU data regarding the polyphyly of Tricharina.  相似文献   
997.
A wide variety of cancer types has been associated with paraneoplastic autoimmune disorders and with the induction of autoimmunity against several autoantigens, among them self-antigens that are also expressed by tumor cells. This raises the question of autoimmune disorders as a result of immune reactions to the tumor. To date, however, requirements for the generation of autoimmune reactions in cancer patients remain largely unclear. In this study, we characterized conditions in altogether 131 patients, which determine autoimmune responses in primary breast cancer patients. We used ex vivo IFN-γ EliSpot assays against autologous tumor or skin lysates to evaluate tumor- and auto-reactive T-cells (TCs) in the bone marrow (BM) as well as ELISA, ECLIA, and turbidimetric immunoassays for the detection of auto-reactive antibodies in the peripheral blood and compared results to intratumoral cytokine concentrations and pathobiological features of the primary tumor tissue. We here demonstrate a significant correlation between anti-tumor BMTC responses and cellular autoimmune reactivity in primary breast cancer patients (P?=?0.002). Humoral autoimmune reactions, however, were negatively correlated with anti-tumor TC immunity (P?=?0.039). We observed auto-reactive BMTCs especially in patients with well-differentiated, hormone receptor-positive carcinomas (P?=?0.009). Furthermore, elevated concentrations of intratumoral IFN-α significantly correlated with the induction of cellular autoimmune reactivity (P?=?0.0002), while humoral autoimmune reactions correlated with increased levels of intratumoral IL-12 (P?=?0.04). Altogether, these data indicate a significant role of the tumor microenvironment and particularly that of IFN-α and IL-12 in the induction of systemic autoimmune responses and imply that the primary tumor tissue represents an integral site of autoimmune regulation in cancer patients.  相似文献   
998.
We conducted a comparative analysis of the root metabolome of six parental maize inbred lines and their 14 corresponding hybrids showing fresh weight heterosis. We demonstrated that the metabolic profiles not only exhibit distinct features for each hybrid line compared with its parental lines, but also separate reciprocal hybrids. Reconstructed metabolic networks, based on robust correlations between metabolic profiles, display a higher network density in most hybrids as compared with the corresponding inbred lines. With respect to metabolite level inheritance, additive, dominant and overdominant patterns are observed with no specific overrepresentation. Despite the observed complexity of the inheritance pattern, for the majority of metabolites the variance observed in all 14 hybrids is lower compared with inbred lines. Deviations of metabolite levels from the average levels of the hybrids correlate negatively with biomass, which could be applied for developing predictors of hybrid performance based on characteristics of metabolite patterns.  相似文献   
999.
Certain types of human papillomaviruses (HPV) are causatively associated with cervical carcinoma, the second most common cancer in women worldwide. Due to limitations in the availability of currently used virus-like particle (VLP)-based vaccines against HPV to women of developing countries, where most cases of cervical cancer occur, the development of a cost-effective second-generation vaccine is a necessity. Capsomeres have recently been demonstrated to be highly immunogenic and to have a number of advantages as a potential cost-effective alternative to VLP-based HPV vaccines. We have expressed a mutated HPV-16 L1 (L1_2xCysM) gene that retained the ability to assemble L1 protein to capsomeres in tobacco chloroplasts. The recombinant protein yielded up to 1.5% of total soluble protein. The assembly of capsomeres was examined and verified by cesium chloride density gradient centrifugation and sucrose sedimentation analysis. An antigen capture enzyme-linked immunosorbent assay confirmed the formation of capsomeres by using a conformation-specific monoclonal antibody which recognized the conformational epitopes. Transplastomic tobacco plants exhibited normal growth and morphology, but all such lines showed male sterility in the T0, T1 and T2 generations. Taken together, these results indicate the possibility of producing a low-cost capsomere-based vaccine by plastids.  相似文献   
1000.
The presence of aerobic anoxygenic phototrophs (AAPs) has been repeatedly reported from various marine environments, but their distribution in freshwater lakes was neglected until recently. We investigated the phylogenetic composition of AAP communities in 10 lakes in Northeastern Germany with different trophic status including oligotrophic Lake Stechlin and humic matter rich Lake Grosse Fuchskuhle. The AAP community was composed by members of Alpha- and Betaproteobacteria, but their contribution varied largely among the studied lakes. Our results show that AAP community composition in the studied lakes was affected mostly by pH and humic matter content. While alkaline lakes were mostly composed of Betaproteobacteria, the acidic and humic matter rich south-west (SW) basin of Lake Grosse Fuchskule was dominated (87%) by Alphaproteobacteria. The most frequent group within Betaproteobacteria was a cluster of pufM genes which was phylogenetically related to Rhodoferax representing 38.5% of all retrieved sequences. Alphaproteobacteria-related sequences had a broader phylogenetic diversity including six different taxa dominated by Sphingomonas- and Rhodobacter-like bacteria in lakes with alkaline to neutral pH. In the acidic and humic matter-rich SW basin of Lake Grosse Fuchskuhle, however, Methylobacterium-related sequences dominated the AAP community. We suggest that the variable AAP community structure might reflect the potential of these bacteria to cope with the contrasting conditions in freshwater environments.  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