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   4744篇
  免费   360篇
  国内免费   3篇
  2023年   14篇
  2022年   45篇
  2021年   89篇
  2020年   66篇
  2019年   107篇
  2018年   120篇
  2017年   103篇
  2016年   156篇
  2015年   229篇
  2014年   291篇
  2013年   338篇
  2012年   423篇
  2011年   427篇
  2010年   236篇
  2009年   195篇
  2008年   298篇
  2007年   311篇
  2006年   282篇
  2005年   227篇
  2004年   217篇
  2003年   223篇
  2002年   170篇
  2001年   37篇
  2000年   41篇
  1999年   53篇
  1998年   58篇
  1997年   33篇
  1996年   41篇
  1995年   41篇
  1994年   22篇
  1993年   27篇
  1992年   22篇
  1991年   15篇
  1990年   16篇
  1989年   17篇
  1988年   8篇
  1987年   8篇
  1986年   13篇
  1985年   10篇
  1984年   10篇
  1983年   12篇
  1982年   7篇
  1981年   8篇
  1980年   4篇
  1978年   3篇
  1977年   3篇
  1976年   6篇
  1975年   6篇
  1973年   3篇
  1969年   4篇
排序方式: 共有5107条查询结果,搜索用时 15 毫秒
151.
Interest in the use of corncobs as feedstock for bioethanol production is growing. This study assesses the feasibility of sequential thermochemical diluted sulfuric acid pretreatment of corncobs at moderate temperature to hydrolyze the hemicellulosic fraction, followed by enzymatic hydrolysis of the whole slurry, and fermentation of the obtained syrup. The total sugar concentration after enzymatic hydrolysis was 85.21 g/l, i.e., 86 % of the sugars were liberated from the polymeric fractions, together with a low amount of furfural (0.26 g/l) and 4.01 g/l of acetic acid. The syrups, which contained 36.3, 40.9, 4.47, and 1.84 g/l of xylose, glucose, arabinose, and mannose, respectively, were fermented (pH 7, 37 °C, 150 rpm) to ethanol with the metabolically engineered acetate-tolerant Escherichia coli strain MS04 under non-aerated conditions, producing 35 g/l of ethanol in 18 h (1.94 gEtOH/l/h), i.e., a conversion yield greater than 80 % of the theoretical value based on total sugars was obtained. Hence, using the procedures developed in this study, 288 l of ethanol can be produced per metric ton of dry corncobs. Strain MS04 can ferment sugars in the presence of acetate, and the amount of furans generated during the sequential thermochemical and enzymatic hydrolysis was low; hence, the detoxification step was avoided. The residual salts, acetic acid, and solubilized lignin present in the syrup did not interfere with the production of ethanol by E. coli MS04 and the results show that this strain can metabolize mixtures of glucose and xylose simultaneously.  相似文献   
152.

Background

Comparisons of objectively measured physical activity (PA) between residents of European countries measured concurrently with the same protocol are lacking. We aimed to compare PA between the seven European countries involved in the Food4Me Study, using accelerometer data collected remotely via the Internet.

Methods

Of the 1607 participants recruited, 1287 (539 men and 748 women) provided at least 3 weekdays and 2 weekend days of valid accelerometer data (TracmorD) at baseline and were included in the present analyses.

Results

Men were significantly more active than women (physical activity level = 1.74 vs. 1.70, p < 0.001). Time spent in light PA and moderate PA differed significantly between countries but only for women. Adherence to the World Health Organization recommendation to accumulate at least 150 min of moderate-equivalent PA weekly was similar between countries for men (range: 54–65%) but differed significantly between countries for women (range: 26–49%). Prevalence estimates decreased substantially for men and women in all seven countries when PA guidelines were defined as achieving 30 min of moderate and vigorous PA per day.

Conclusions

We were able to obtain valid accelerometer data in real time via the Internet from 80% of participants. Although our estimates are higher compared with data from Sweden, Norway, Portugal and the US, there is room for improvement in PA for all countries involved in the Food4Me Study.  相似文献   
153.

Objective

Human tumor cell lines form the basis of the majority of present day laboratory cancer research. These models are vital to studying the molecular biology of tumors and preclinical testing of new therapies. When compared to traditional adherent cell lines, suspension cell lines recapitulate the genetic profiles and histologic features of glioblastoma multiforme (GBM) with higher fidelity. Using a modified neural stem cell culture technique, here we report the characterization of GBM cell lines including GBM variants.

Methods

Tumor tissue samples were obtained intra-operatively and cultured in neural stem cell conditions containing growth factors. Tumor lines were characterized in vitro using differentiation assays followed by immunostaining for lineage-specific markers. In vivo tumor formation was assayed by orthotopic injection in nude mice. Genetic uniqueness was confirmed via short tandem repeat (STR) DNA profiling.

Results

Thirteen oncosphere lines derived from GBM and GBM variants, including a GBM with PNET features and a GBM with oligodendroglioma component, were established. All unique lines showed distinct genetic profiles by STR profiling. The lines assayed demonstrated a range of in vitro growth rates. Multipotency was confirmed using in vitro differentiation. Tumor formation demonstrated histologic features consistent with high grade gliomas, including invasion, necrosis, abnormal vascularization, and high mitotic rate. Xenografts derived from the GBM variants maintained histopathological features of the primary tumors.

Conclusions

We have generated and characterized GBM suspension lines derived from patients with GBMs and GBM variants. These oncosphere cell lines will expand the resources available for preclinical study.  相似文献   
154.
The franciscana dolphin, Pontorporia blainvillei, is an endemic cetacean of the Atlantic coast of South America. Its coastal distribution and restricted movement patterns make this species vulnerable to anthropogenic factors, particularly to incidental bycatch. We used mitochondrial DNA control region sequences, 10 microsatellites, and sex data to investigate the population structure of the franciscana dolphin from a previously established management area, which includes the southern edge of its geographic range. F‐statistics and Bayesian cluster analyses revealed the existence of three genetically distinct populations. Based on the microsatellite loci, similar levels of genetic variability were found in the area; 13 private alleles were found in Monte Hermoso, but none in Claromecó. When considering the mitochondrial DNA control region sequences, lower levels of genetic diversity were found in Monte Hermoso, when compared to the other localities. Low levels of gene flow were found between most localities. Additionally, no evidence of isolation by distance nor sex‐biased dispersal was detected in the study area. In view of these results showing that populations from Necochea/Claromecó, Monte Hermoso, and Río Negro were found to be genetically distinct and the available genetic information for the species previously published, Argentina would comprise five distinct populations: Samborombón West/Samborombón South, Cabo San Antonio/Buenos Aires East, Necochea/Claromecó/Buenos Aires Southwest, Monte Hermoso, and Río Negro. In order to ensure the long‐term survival of the franciscana dolphin, management and conservation strategies should be developed considering each of these populations as different management units.  相似文献   
155.
The azoles are the class of medications most commonly used to fight infections caused by Candida sp. Typically, resistance can be attributed to mutations in ERG11 gene (CYP51) which encodes the cytochrome P450 14α-demethylase, the primary target for the activity of azoles. The objective of this study was to identify mutations in the coding region of theERG11 gene in clinical isolates of Candidaspecies known to be resistant to azoles. We identified three new synonymous mutations in the ERG11 gene in the isolates of Candida glabrata (C108G, C423T and A1581G) and two new nonsynonymous mutations in the isolates of Candida krusei - A497C (Y166S) and G1570A (G524R). The functional consequence of these nonsynonymous mutations was predicted using evolutionary conservation scores. The G524R mutation did not have effect on 14α-demethylase functionality, while the Y166S mutation was found to affect the enzyme. This observation suggests a possible link between the mutation and dose-dependent sensitivity to voriconazole in the clinical isolate of C. krusei. Although the presence of the Y166S in phenotype of reduced azole sensitivity observed in isolate C. kruseidemands investigation, it might contribute to the search of new therapeutic agents against resistant Candida isolates.  相似文献   
156.
157.
Early social conditions are vital for the establishment of future social interactions. Less, however, is known about how differences in early social conditions contribute to the process of individual recognition and subsequently in the decision of associating and exploring behaviours. In this study, we address this gap in the Trinidadian guppy Poecilia reticulata and test the prediction that fish would show a higher tendency to recognize and associate with individuals of similar phenotype. This prediction was tested by comparing the likelihood of association and latency to explore a novel area in males and females when in the presence of individuals that were familiar (reared together but from different populations), from the same population of origin (from the same population but deprived of interaction with each other), or were unfamiliar (different population and have never interacted). Both early social conditions and population of origin (phenotype matching) affected the tendency to shoal and explore. Females, but not males, exhibited identical preference to associate either with unfamiliar females as with familiar females from a different population. Importantly, female preference did not occur with unfamiliar individuals from a different population. In contrast with our prediction, tendency to shoal did not predict exploration propensity. Males always start exploration before the group whenever unfamiliar males composed the group. Females on the other hand only moved to the novel area after seeing the group doing so, revealing sexual dimorphism in exploratory behaviour. Our results provide evidence for a familiarity and phenotypic matching recognition mechanism at the population level and also highlight the importance of accounting for differences between sexes when investigating the effects of early social conditions.  相似文献   
158.
The present study evaluated biofilm growth in AISI 316L stainless steel tubes for seawater-cooled exchanger-condensers that had four different arithmetic mean surface roughness values ranging from 0.14 μm to 1.2 μm. The results of fluid frictional resistance and heat transfer resistance regarding biofilm formation in the roughest surface showed increases of 28.2% and 19.1% respectively, compared with the smoothest surface. The biofilm thickness taken at the end of the experiment showed variations of up to 74% between the smoothest and roughest surfaces. The thermal efficiency of the heat transfer process in the tube with the roughest surface was 17.4% greater than that in the tube with the smoothest surface. The results suggest that the finish of the inner surfaces of the tubes in heat exchanger-condensers is critical for improving energy efficiency and avoiding biofilm adhesion. This may be utilised to reduce biofilm adhesion and growth in the design of heat exchanger-condensers.  相似文献   
159.
The recruitment of tissue‐resident stem cells is important for wound regeneration. Periodontal ligament cells (PDL cells) are heterogeneous cell populations with stemness features that migrate into wound sites to regenerate periodontal fibres and neighbouring hard tissues. Cell migration is regulated by the local microenvironment, coordinated by growth factors and the extracellular matrix (ECM). Integrin‐mediated cell adhesion to the ECM provides essential signals for migration. We hypothesized that PDL cell migration could be enhanced by selective expression of integrins. The migration of primary cultured PDL cells was induced by platelet‐derived growth factor‐BB (PDGF‐BB). The effects of blocking specific integrins on migration and ECM adhesion were investigated based on the integrin expression profiles observed during migration. Up‐regulation of integrins α3, α5, and fibronectin was identified at distinct localizations in migrating PDL cells. Treatment with anti‐integrin α5 antibodies inhibited PDL cell migration. Treatment with anti‐integrin α3, α3‐blocking peptide, and α3 siRNA significantly enhanced cell migration, comparable to treatment with PDGF‐BB. Furthermore, integrin α3 inhibition preferentially enhanced adhesion to fibronectin via integrin α5. These findings indicate that PDL cell migration is reciprocally regulated by integrin α3‐mediated inhibition and α5‐mediated promotion. Thus, targeting integrin expression is a possible therapeutic strategy for periodontal regeneration.  相似文献   
160.
Acromegaly is a rare disease resulting from hypersecretion of growth hormone (GH) and insulin‐like growth factor 1 (IGF1) typically caused by pituitary adenomas, which is associated with increased mortality and morbidity. Somatostatin analogues (SSAs) represent the primary medical therapy for acromegaly and are currently used as first‐line treatment or as second‐line therapy after unsuccessful pituitary surgery. However, a considerable proportion of patients do not adequately respond to SSAs treatment, and therefore, there is an urgent need to identify biomarkers predictors of response to SSAs. The aim of this study was to examine E‐cadherin expression by immunohistochemistry in fifty‐five GH‐producing pituitary tumours and determine the potential association with response to SSAs as well as other clinical and histopathological features. Acromegaly patients with tumours expressing low E‐cadherin levels exhibit a worse response to SSAs. E‐cadherin levels are associated with GH‐producing tumour histological subtypes. Our results indicate that the immunohistochemical detection of E‐cadherin might be useful in categorizing acromegaly patients based on the response to SSAs.  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