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   13943篇
  免费   1296篇
  国内免费   7篇
  2022年   95篇
  2021年   227篇
  2020年   122篇
  2019年   166篇
  2018年   227篇
  2017年   201篇
  2016年   296篇
  2015年   524篇
  2014年   634篇
  2013年   753篇
  2012年   1021篇
  2011年   1021篇
  2010年   670篇
  2009年   590篇
  2008年   818篇
  2007年   796篇
  2006年   742篇
  2005年   682篇
  2004年   720篇
  2003年   655篇
  2002年   659篇
  2001年   153篇
  2000年   106篇
  1999年   154篇
  1998年   181篇
  1997年   118篇
  1996年   95篇
  1995年   92篇
  1994年   124篇
  1993年   110篇
  1992年   123篇
  1991年   99篇
  1990年   91篇
  1989年   86篇
  1988年   70篇
  1987年   79篇
  1986年   76篇
  1985年   104篇
  1984年   129篇
  1983年   80篇
  1982年   122篇
  1981年   91篇
  1980年   85篇
  1979年   71篇
  1978年   81篇
  1977年   63篇
  1976年   70篇
  1975年   65篇
  1974年   73篇
  1973年   64篇
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.

Background

The ability to discriminate between two similar or progressively dissimilar colours is important for many animals as it allows for accurately interpreting visual signals produced by key target stimuli or distractor information. Spectrophotometry objectively measures the spectral characteristics of these signals, but is often limited to point samples that could underestimate spectral variability within a single sample. Algorithms for RGB images and digital imaging devices with many more than three channels, hyperspectral cameras, have been recently developed to produce image spectrophotometers to recover reflectance spectra at individual pixel locations. We compare a linearised RGB and a hyperspectral camera in terms of their individual capacities to discriminate between colour targets of varying perceptual similarity for a human observer.

Main Findings

(1) The colour discrimination power of the RGB device is dependent on colour similarity between the samples whilst the hyperspectral device enables the reconstruction of a unique spectrum for each sampled pixel location independently from their chromatic appearance. (2) Uncertainty associated with spectral reconstruction from RGB responses results from the joint effect of metamerism and spectral variability within a single sample.

Conclusion

(1) RGB devices give a valuable insight into the limitations of colour discrimination with a low number of photoreceptors, as the principles involved in the interpretation of photoreceptor signals in trichromatic animals also apply to RGB camera responses. (2) The hyperspectral camera architecture provides means to explore other important aspects of colour vision like the perception of certain types of camouflage and colour constancy where multiple, narrow-band sensors increase resolution.  相似文献   
992.
Cell competition where ‘loser’ cells are eliminated by neighbors with higher fitness is a widespread phenomenon in development. However, a growing body of evidence argues cells with somatic mutations compete with their wild type counterparts in the earliest stages of cancer development. Recent studies have begun to shed light on the molecular and cellular mechanisms that alter the competitiveness of cells carrying somatic mutations in adult tissues. Cells with a ‘winner’ phenotype create clones which may expand into extensive fields of mutant cells within normal appearing epithelium, favoring the accumulation of further genetic alterations and the evolution of cancer. Here we focus on how mutations which disrupt the Notch signaling pathway confer a ‘super competitor’ status on cells in squamous epithelia and consider the broader implications for cancer evolution.  相似文献   
993.
BackgroundBarrett''s esophagus (BE) is a commonly undiagnosed condition that predisposes to esophageal adenocarcinoma. Routine endoscopic screening for BE is not recommended because of the burden this would impose on the health care system. The objective of this study was to determine whether a novel approach using a minimally invasive cell sampling device, the Cytosponge, coupled with immunohistochemical staining for the biomarker Trefoil Factor 3 (TFF3), could be used to identify patients who warrant endoscopy to diagnose BE.ConclusionsThe Cytosponge-TFF3 test is safe and acceptable, and has accuracy comparable to other screening tests. This test may be a simple and inexpensive approach to identify patients with reflux symptoms who warrant endoscopy to diagnose BE.  相似文献   
994.
Computation has become a critical component of research in biology. A risk has emerged that computational and programming challenges may limit research scope, depth, and quality. We review various solutions to common computational efficiency problems in ecological and evolutionary research. Our review pulls together material that is currently scattered across many sources and emphasizes those techniques that are especially effective for typical ecological and environmental problems. We demonstrate how straightforward it can be to write efficient code and implement techniques such as profiling or parallel computing. We supply a newly developed R package (aprof) that helps to identify computational bottlenecks in R code and determine whether optimization can be effective. Our review is complemented by a practical set of examples and detailed Supporting Information material (S1S3 Texts) that demonstrate large improvements in computational speed (ranging from 10.5 times to 14,000 times faster). By improving computational efficiency, biologists can feasibly solve more complex tasks, ask more ambitious questions, and include more sophisticated analyses in their research.
This is part of the PLOS Computational Biology Education collection.
  相似文献   
995.
Yeast pseudohyphal filamentation is a stress-responsive growth transition relevant to processes required for virulence in pathogenic fungi. Pseudohyphal growth is controlled through a regulatory network encompassing conserved MAPK (Ste20p, Ste11p, Ste7p, Kss1p, and Fus3p), protein kinase A (Tpk2p), Elm1p, and Snf1p kinase pathways; however, the scope of these pathways is not fully understood. Here, we implemented quantitative phosphoproteomics to identify each of these signaling networks, generating a kinase-dead mutant in filamentous S. cerevisiae and surveying for differential phosphorylation. By this approach, we identified 439 phosphoproteins dependent upon pseudohyphal growth kinases. We report novel phosphorylation sites in 543 peptides, including phosphorylated residues in Ras2p and Flo8p required for wild-type filamentous growth. Phosphoproteins in these kinase signaling networks were enriched for ribonucleoprotein (RNP) granule components, and we observe co-localization of Kss1p, Fus3p, Ste20p, and Tpk2p with the RNP component Igo1p. These kinases localize in puncta with GFP-visualized mRNA, and KSS1 is required for wild-type levels of mRNA localization in RNPs. Kss1p pathway activity is reduced in lsm1Δ/Δ and pat1Δ/Δ strains, and these genes encoding P-body proteins are epistatic to STE7. The P-body protein Dhh1p is also required for hyphal development in Candida albicans. Collectively, this study presents a wealth of data identifying the yeast phosphoproteome in pseudohyphal growth and regulatory interrelationships between pseudohyphal growth kinases and RNPs.  相似文献   
996.

Background

Despite being a recognized standard of tuberculosis (TB) care internationally, mandatory TB case notification brings forth challenges from the private sector. Only three TB cases were notified in 2013 by private practitioners compared to 2000 TB cases notified yearly from the public sector in Alappuzha district. The study objective was to explore the knowledge, opinion and barriers regarding TB Notification among private practitioners offering TB services in Alappuzha, Kerala state, India.

Methods & Findings

This was a mixed-methods study with quantitative (survey) and qualitative components conducted between December 2013 and July 2014. The survey, using a structured questionnaire, among 169 private practitioners revealed that 88% were aware of mandatory notification. All patient-related details requested in the notification form (except government-issued identification number) were perceived to be important and easy to provide by more than 80% of practitioners. While more than 95% felt that notification should be mandatory, punitive action in case of failure to notify was considered unnecessary by almost two third. General practitioners (98%) were more likely to be aware of notification than specialists (84 %). (P<0.01). Qualitative purposive personal interviews (n=34) were carried out among private practitioners and public health providers. On thematic framework analysis of the responses, barriers to TB notification were grouped into three themes: ‘private provider misconceptions about notification’, ‘patient confidentiality, and stigma and discrimination ’and ‘lack of cohesion and coordination between public and private sector’. Private practitioners did not consider it necessary to notify TB cases treated with daily regimen.

Conclusion

Communication strategies like training, timely dissemination of information of policy changes and one-to-one dialogue with private practitioners to dispel misconceptions may enhance TB notification. Trust building strategies like providing feedback about referred cases from private sector, health personnel visit or a liaison private doctor may ensure compliance to public health activities.  相似文献   
997.
The effect of hydrogen sulfide (H2S) on differentiation of 3T3L1-derived adipocytes was examined. Endogenous H2S was increased after 3T3L1 differentiation. The expression of the H2S-synthesising enzymes, cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST), was increased in a time-dependent manner during 3T3L1 differentiation. Expression of genes associated with adipogenesis related genes including fatty acid binding protein 4 (FABP4/aP2), a key regulator of this process, was increased by GYY4137 (a slow-releasing H2S donor compound) and sodium hydrosulfide (NaHS, a classical H2S donor) but not by ZYJ1122 or time-expired NaHS. Furthermore expression of these genes were reduced by aminooxyacetic acid (AOAA, CBS inhibitor), DL-propargylglycine (PAG, CSE inhibitor) as well as by CSE small interference RNA (siCSE) and siCBS. The size and number of lipid droplets in mature adipocytes was significantly increased by both GYY4137 and NaHS, which also impaired the ability of CL316,243 (β3-agonist) to promote lipolysis in these cells. In contrast, AOAA and PAG had the opposite effect. Taken together, we show that the H2S-synthesising enzymes CBS, CSE and 3-MST are endogenously expressed during adipogenesis and that both endogenous and exogenous H2S modulate adipogenesis and adipocyte maturation.  相似文献   
998.
999.
This study tests the hypothesis that high levels of high-frequency heart rate variability (HF-HRV) predisposes individuals to affiliate with new groups. Resting cardiac physiological recordings were taken before and after experimental sessions to measure trait high-frequency heart rate variability as an index of dispositional autonomic influence on heart rate. Following an experimental manipulation of priming of caring-related words, participants engaged in a minimal group paradigm, in which they imagined being a member of one of two arbitrary groups, allocated money to members of the two groups, and rated their affiliation with the groups. High levels of HF-HRV were associated with ingroup favouritism while allocating money, an effect largely attributable to a positive relationship between HF-HRV and allocation of money to the ingroup, and less due to a negative relationship between HF-HRV and money allocation to the outgroup. HF-HRV was also associated with increased self-reported affiliation feelings for the ingroup but was unrelated to feelings towards the outgroup. These effects remained substantial even after controlling for age, gender, BMI, mood, caffeine consumption, time of day of data collection, smoking and alcohol behaviour, and respiration rate. Further, the effects were observed regardless of whether participants were primed with caring-related words or not. This study is the first to bridge a long history of research on ingroup favouritism to the relatively recent body of research on cardiac vagal tone by uncovering a positive association between HF-HRV and affiliation with a novel group.  相似文献   
1000.
Lymph node and spleen cells of mice doubly immunized by epicutaneous and intravenous hapten application produce a suppressive component that inhibits the action of the effector T cells that mediate contact sensitivity reactions. We recently re-investigated this phenomenon in an immunological system. CD8+ T lymphocyte-derived exosomes transferred suppressive miR-150 to the effector T cells antigen-specifically due to exosome surface coat of antibody light chains made by B1a lymphocytes. Extracellular RNA (exRNA) is protected from plasma RNases by carriage in exosomes or by chaperones. Exosome transfer of functional RNA to target cells is well described, whereas the mechanism of transfer of exRNA free of exosomes remains unclear. In the current study we describe extracellular miR-150, extracted from exosomes, yet still able to mediate antigen-specific suppression. We have determined that this was due to miR-150 association with antibody-coated exosomes produced by B1a cell companions of the effector T cells, which resulted in antigen-specific suppression of their function. Thus functional cell targeting by free exRNA can proceed by transfecting companion cell exosomes that then transfer RNA cargo to the acceptor cells. This contrasts with the classical view on release of RNA-containing exosomes from the multivesicular bodies for subsequent intercellular targeting. This new alternate pathway for transfer of exRNA between cells has distinct biological and immunological significance, and since most human blood exRNA is not in exosomes may be relevant to evaluation and treatment of diseases.  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