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   3174篇
  免费   186篇
  国内免费   1篇
  3361篇
  2023年   35篇
  2022年   61篇
  2021年   117篇
  2020年   85篇
  2019年   89篇
  2018年   129篇
  2017年   117篇
  2016年   128篇
  2015年   190篇
  2014年   222篇
  2013年   250篇
  2012年   247篇
  2011年   232篇
  2010年   139篇
  2009年   112篇
  2008年   151篇
  2007年   125篇
  2006年   144篇
  2005年   114篇
  2004年   100篇
  2003年   89篇
  2002年   89篇
  2001年   62篇
  2000年   37篇
  1999年   44篇
  1998年   16篇
  1997年   8篇
  1996年   17篇
  1995年   5篇
  1994年   15篇
  1993年   6篇
  1992年   17篇
  1991年   13篇
  1990年   13篇
  1989年   10篇
  1988年   14篇
  1987年   13篇
  1986年   11篇
  1985年   15篇
  1984年   14篇
  1983年   10篇
  1981年   8篇
  1980年   6篇
  1979年   10篇
  1978年   3篇
  1977年   3篇
  1976年   3篇
  1975年   6篇
  1974年   3篇
  1966年   3篇
排序方式: 共有3361条查询结果,搜索用时 15 毫秒
971.
In this article, we present and discuss an alternative for data analysis of the metabolic profiles of both healthy Eucalyptus globulus and those infected with the Mycosphaerella leaf disease. The crude extracts were analyzed by reversed-phase ultra performance liquid chromatography-mass spectrometry. In order to glean the most useful information from these complex measurements, parallel factor analysis (PARAFAC) was employed for pattern recognition. After PARAFAC modeling, inspection of the scores and loadings graph allowed distinction of the healthy from the infected E. globulus samples and determination of biomarkers related to the biotic stress. The assessment of the monoisotopic masses and the fragmentation patterns allowed the identification of these biomarkers. It is hoped that the proposed method can be used for the diagnosis of diseases in plants, as well as to provide additional insight into the plant’s defense mechanism. Potentially, this may demonstrate the advantages of employing high order chemometric techniques in metabolomic data analysis.  相似文献   
972.
Sporotrichosis is a polymorphic disease caused by a complex of thermodimorphic fungi including S. brasiliensis, S. schenckii sensu stricto (s. str.), S. globosa and S. luriei. Humans and animals can acquire the disease through traumatic inoculation of propagules into the subcutaneous tissue. Despite the importance of sporotrichosis as a disease that can take epidemic proportions there are just a few studies dealing with genetic polymorphisms and genomic architecture of these pathogens. The main objective of this study was to investigate chromosomal polymorphisms and genomic organization among different isolates in the S. schenckii complex. We used pulsed field gel electrophoresis (PFGE) to separate chromosomal fragments of isolated DNA, followed by probe hybridization. Nine loci (β-tubulin, calmodulin, catalase, chitin synthase 1, Internal Transcribed Spacer, Pho85 cyclin-dependent kinase, protein kinase C Ss-2, G protein α subunit and topoisomerase II) were mapped onto chromosomal bands of Brazilian isolates of S. schenckii s. str. and S. brasiliensis. Our results revealed the presence of intra and interspecies polymorphisms in chromosome number and size. The gene hybridization analysis showed that closely related species in phylogenetic analysis had similar genetic organizations, mostly due to identification of synteny groups in chromosomal bands of similar sizes. Our results bring new insights into the genetic diversity and genome organization among pathogenic species in the Sporothrix schenckii complex.  相似文献   
973.

Introduction

As population ageing becomes a global phenomenon the need to understand the quality of life of older people around the world has become increasingly salient. The CASP-19 is a well established measure of quality of later life. The scale is composed of 19 items which map onto the four domains of control (C), Autonomy (A), Self-Realisation (S) and Pleasure (P). It has already been translated to 12 languages and has been used in a number of national and international studies. However use of the scale outside of Europe has been very limited. The objective of this study was to translate and evaluate the use of the CASP-19 amongst older Brazilians.

Methods

The CASP-19 was translated from English to Portuguese, back-translated and submitted to an analysis of equivalence by a committee of judges. The scale was then administered to a sample of community dwelling older people in Recife, Brazil (n = 87), and tested for psychometric properties. The Control and Pleasure domains exhibited good internal consistency. By removing one item from each of the Autonomy and Self Realisation domains their internal consistency was improved.

Results

The mean age of the sample was 75.6±0.7 years, subjects were mainly female (52.9%), white (52.9%), who lived without a partner (54%), and had a monthly income varying from USD 340.00 to USD 850.00. Translation and cross-cultural adaptation permitted good understanding and applicability of final version. Psychometric analyses revealed that the removal of two items improved the internal consistency of the Autonomy and Pleasure domains. Confirmatory factor analyses suggest that a 16 item, four factor, model best fits the data.

Conclusion

In this small exploratory study the CASP-19 Brazil demonstrated good psychometric properties. It was easy to use for both participants and researchers. Hopefully future studies in Brazil will employ the scale so that more direct cross national comparisons can be made with older people in Europe and the US.  相似文献   
974.
Inosine, a naturally occurring purine formed from the breakdown of adenosine, is associated with immunoregulatory effects. Evidence shows that inosine modulates lung inflammation and regulates cytokine generation. However, its role in controlling allergen-induced lung inflammation has yet to be identified. In this study, we aimed to investigate the role of inosine and adenosine receptors in a murine model of lung allergy induced by ovalbumin (OVA). Intraperitoneal administration of inosine (0.001–10 mg/kg, 30 min before OVA challenge) significantly reduced the number of leukocytes, macrophages, lymphocytes and eosinophils recovered in the bronchoalveolar lavage fluid of sensitized mice compared with controls. Interestingly, our results showed that pre-treatment with the selective A2A receptor antagonist (ZM241385), but not with the selective A2B receptor antagonist (alloxazine), reduced the inhibitory effects of inosine against macrophage count, suggesting that A2A receptors mediate monocyte recruitment into the lungs. In addition, the pre-treatment of mice with selective A3 antagonist (MRS3777) also prevented inosine effects against macrophages, lymphocytes and eosinophils. Histological analysis confirmed the effects of inosine and A2A adenosine receptors on cell recruitment and demonstrated that the treatment with ZM241385 and alloxazine reverted inosine effects against mast cell migration into the lungs. Accordingly, the treatment with inosine reduced lung elastance, an effect related to A2 receptors. Moreover, inosine reduced the levels of Th2-cytokines, interleukin-4 and interleukin-5, an effect that was not reversed by A2A or A2B selective antagonists. Our data show that inosine acting on A2A or A3 adenosine receptors can regulate OVA-induced allergic lung inflammation and also implicate inosine as an endogenous modulator of inflammatory processes observed in the lungs of asthmatic patients.  相似文献   
975.
Bent metallocenes are a class of organometallic compounds that are widely used as catalysts in olefin polymerization procedures. We found a linear relation between the relative stability of bent titanocenes and the average delocalization index (DI) for Ti–C (from the cyclopentadienyl ring) atomic pairs within the evaluated compounds. As a consequence, the stability of the bent titanocenes can be estimated from their topologies. However, secondary interactions between the ligands of some of the bent titanocenes reduce the coefficient of determination for the average DI–stability relation.
Figure
Molecular graph of one of the bent titanocenes studied in this work, and a plot showing the linear relation between the delocalization index (DI) of Ti–C (from the π-ligand) and the stability of the corresponding bent titanocene  相似文献   
976.
Abstract

Matricaria chamomilla L. contains antioxidant flavonoids that can have their bioactivity enhanced by enzymatic hydrolysis of specific glycosyl groups. This study implements an untargeted metabolomics approach based on ultra-performance liquid chromatography coupled with electrospray ionisation quadrupole time-of-flight mass spectrometry technique operating in MSE mode (UPLC-QTOF-MSE) and spectrophotometric analysis of chamomile aqueous infusions, before and after hydrolysis by hesperidinase and β-galactosidase. Several phenolic compounds were altered in the enzymatically treated infusion, with the majority being flavonoid derivatives of apigenin, esculetin, and quercetin. Although enzymatically modifying the infusion only led to a small increase in antioxidant activity (DPPH? method), its inhibitory effect on pancreatic lipase was of particular interest. The enzymatically treated infusion exhibited a greater inhibitory effect (EC50 of 35.6?µM) than unmodified infusion and kinetic analysis suggested mixed inhibition of pancreatic lipase. These results are of great relevance due to the potential of enzymatically treated functional foods in human health.  相似文献   
977.
Trichogenes longipinnis Britski & Ortega is a narrowly distributed endemic and phenotypically variable catfish from the coastal basins of the Serra do Mar range in southeast Brazil. We examined patterns of mtDNA variation of this species in coastal basins of the Serra do Mar to determine the influences of past climatic and geomorphological processes in connection with the currently isolated basins. Allozyme data were also used to test the hypothesis that the different spotting patterns in the different areas could be the result of cryptic speciation. Regardless of body pigmentation, T. longipinnis specimens from across the basins were found to belong to a single species, but the populations were structured in accordance with the current hydrological watersheds, in four management units across the three distinct basins of its geographic distribution. Thus, the current genetic distribution may be best explained by both marine regressions and orogeny. Based on the low levels of genetic variation and high population structure observed, we suggest that T. longipinnis should be classified as “vulnerable” in the Brazilian red list of threatened fauna. Furthermore, we propose that the headwaters of the Parati-Mirim River basin should be incorporated as an extension of the Bocaina National Park to protect its genetically differentiated lineages.  相似文献   
978.
The boll weevil Anthonomus grandis Boheman (Coleoptera: Curculionidae) is the most important cotton pest in Brazil. A large-scale field-testing of a Boll Weevil Suppression Program (BWSP) was implemented to assess its technical and operational feasibility for boll weevil suppression in the state of Goiás, Brazil. The pilot plan focused on 3,608 ha of cotton during the 2006/2007 and 6,011 ha in the 2007/2008 growing seasons; the areas were divided into four inner zones with an outer buffer zone. We analyzed data on boll weevil captures using pheromone traps installed in the BWSP fields, on the detection of the first insect and the first damaged floral bud, greatest damage, and number of insecticide applications. The nonparametric Mann–Whitney U test was used to evaluate the differences between presuppression and suppression years. Fourteen pheromone-baited trapping evaluations were used to compare the weevil populations from 2006/2007 and 2007/2008 growing seasons. The BWSP regime reduced in-season boll weevil captures from 15- to 500-fold compared to presuppression levels in the preceding year. The low capture rates were related to delays in infestation and damage by weevils. The smaller population size measured by trapping and field monitoring reduced the number of required insecticide treatments. The BWSP strategy was efficient in suppressing populations of this pest and is a viable program for cotton production in subtropical and tropical regions, with long-term economic and environmental benefits.  相似文献   
979.
Enalapril maleate (EM) is a widely used anti-hypertensive drug which is unstable when mixed with excipients. Enalaprilate and diketopiperazine (DPK) are the main degradation products of enalapril. The in situ preparation of enalapril sodium salt (NaE) has been used to improve drug stability in dosage forms; however, gas release and product rejection ensue when the chemical reaction for obtaining the sodium salt is not completely finished before packaging. This study evaluated the effect of stearic acid (SA) on enalapril stability in microcrystalline cellulose (MCC) pellets containing EM or NaE. MCC pellets containing SA were prepared by the extrusion–spheronization technique and characterized. Enalapril stability and dissolution were then evaluated. DPK and enalaprilate formation were reduced by the addition of SA in pellets containing EM. The overall enalapril degradation in these formulations was lower when compared with pellets containing EM or even NaE prepared without SA. The immediate-release characteristic was maintained by the addition of 5% crospovidone to all the formulations tested. The incorporation of SA into NaE pellets resulted in unexpected enalapril degradation, caused by the interaction of these compounds, as suggested by a thermal analysis of the SA–NaE binary mixture. The findings presented here showed that formulations containing SA could substitute the formation of NaE, since they provide better enalapril stability in solid dosage forms. In addition, it is suggested that the stabilization effects would be observed for other N-carboxyalkyl dipeptide analogs with angiotensin converting enzyme inhibition activity, since these new entities share the same degradation pathway of enalapril.  相似文献   
980.
Amylin is a pancreatic hormone that plays important roles in overall metabolism and in glucose homeostasis. The therapeutic restoration of postprandial and basal amylin levels is highly desirable for patients with diabetes who need to avoid glucose excursions. Protein conjugation with polyethylene glycol (PEG) has long been known to be a convenient approach for extending the biological effects of biopharmaceuticals. We have investigated the reactivity of amylin with methoxy polyethylene glycol succinimidyl carbonate and methoxy polyethylene glycol succinimidyl propionate, which have an average molecular weight of 5 kDa. The reaction, which was conducted in both aqueous and organic (dimethyl sulfoxide) solvents, occurred within a few minutes and resulted in at least four detectable products with distinct kinetic phases. These results suggest a kinetic selectivity for PEGylation by succinimidyl derivatives; these derivatives exhibit enhanced reactivity with primary amine groups, as indicated by an evaluation of the remaining amino groups using fluorescamine. The analysis of tryptic fragments from mono- and diPEGylated amylin revealed that conjugation occurred within the 1-11 amino acid region, most likely at the two amine groups of Lys1. The reaction products were efficiently separated by C-18 reversed phase chromatography. Binding assays confirmed the ability of mono- and diPEGylated amylin to interact with the amylin co-receptor receptor activity-modifying protein 2. Subcutaneous administration in mice revealed the effectiveness of monoPEG-amylin and diPEG-amylin in reducing glycemia; both compounds exhibited prolonged action compared to unmodified amylin. These features suggest the potential use of PEGylated amylin to restore basal amylin levels.  相似文献   
[首页] « 上一页 [93] [94] [95] [96] [97] 98 [99] [100] 下一页 » 末  页»
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