全文获取类型
收费全文 | 2756篇 |
免费 | 252篇 |
专业分类
3008篇 |
出版年
2023年 | 18篇 |
2022年 | 38篇 |
2021年 | 59篇 |
2020年 | 31篇 |
2019年 | 34篇 |
2018年 | 49篇 |
2017年 | 51篇 |
2016年 | 88篇 |
2015年 | 147篇 |
2014年 | 158篇 |
2013年 | 182篇 |
2012年 | 236篇 |
2011年 | 207篇 |
2010年 | 144篇 |
2009年 | 131篇 |
2008年 | 186篇 |
2007年 | 161篇 |
2006年 | 149篇 |
2005年 | 169篇 |
2004年 | 169篇 |
2003年 | 148篇 |
2002年 | 135篇 |
2001年 | 46篇 |
2000年 | 28篇 |
1999年 | 32篇 |
1998年 | 31篇 |
1997年 | 20篇 |
1996年 | 11篇 |
1995年 | 15篇 |
1994年 | 15篇 |
1993年 | 16篇 |
1992年 | 13篇 |
1991年 | 12篇 |
1990年 | 11篇 |
1989年 | 8篇 |
1988年 | 15篇 |
1987年 | 6篇 |
1986年 | 4篇 |
1985年 | 5篇 |
1984年 | 3篇 |
1982年 | 7篇 |
1980年 | 2篇 |
1979年 | 3篇 |
1978年 | 2篇 |
1976年 | 3篇 |
1975年 | 1篇 |
1973年 | 1篇 |
1972年 | 3篇 |
1971年 | 1篇 |
1969年 | 1篇 |
排序方式: 共有3008条查询结果,搜索用时 15 毫秒
41.
Mirelle E. E. Br?ker Zarina S. Lalmahomed Henk P. Roest Nick A. van Huizen Lennard J. M. Dekker Wim Calame Cornelis Verhoef Jan N. M. IJzermans Theo M. Luider 《PloS one》2013,8(8)
Introduction
For both patients and the outpatient clinic the frequent follow-up visits after a resection of colorectal cancer (CRC) are time consuming and due to large patient numbers expensive. Therefore it is important to develop an effective non-invasive test for the detection of colorectal liver metastasis (CRLM) which could be used outside the hospital. The urine proteome is known to provide detailed information for monitoring changes in the physiology of humans. Urine collection is non-invasive and urine naturally occurring peptides (NOPs) have the advantage of being easily accessible without labour-intensive sample preparation. These advantages make it potentially useful for a quick and reliable application in clinical settings. In this study, we will focus on the identification and validation of urine NOPs to discriminate patients with CRLM from healthy controls.Materials and Methods
Urine samples were collected from 24 patients with CRLM and 25 healthy controls. In the first part of the study, samples were measured with a nano liquid chromatography (LC) system (Thermo Fisher Scientific, Germaring, Germany) coupled on-line to a hybrid linear ion trap/Orbitrap mass spectrometer (LTQ-Orbitrap-XL, Thermo Fisher Scientific, Bremen, Germany). A discovery set was used to construct the model and consecutively the validation set, being independent from the discovery set, to check the acquired model. From the peptides which were selected, multiple reaction monitoring (MRM''s) were developed on a UPLC-MS/MS system.Results
Seven peptides were selected and applied in a discriminant analysis a sensitivity of 84.6% and a specificity of 92.3% were established (Canonical correlation:0.797, Eigenvalue:1.744, F:4.49, p:0.005). The peptides AGPP(-OH)GEAGKP(-OH)GEQGVP(-OH)GDLGA P(-OH)GP and KGNSGEP(-OH)GAPGSKGDTGAKGEP(-OH)GPVG were selected for further quantitative analysis which showed a sensitivity of 88% and a specificity of 88%.Conclusion
Urine proteomic analysis revealed two very promising peptides, both part from collagen type 1, AGPP(-OH)GEAGKP(-OH)GEQGVP(-OH)GDLGAP(-OH)GP and KGNSGEP(-OH)GAPGSKGDTGAKGEP(-OH)GPVG which could detect CRLM in a non-invasive manner. 相似文献42.
Rémy Crassard Michael D. Petraglia Nick A. Drake Paul Breeze Bernard Gratuze Abdullah Alsharekh Mounir Arbach Huw S. Groucutt Lamya Khalidi Nils Michelsen Christian J. Robin Jérémie Schiettecatte 《PloS one》2013,8(7)
The Arabian Peninsula is a key region for understanding climate change and human occupation history in a marginal environment. The Mundafan palaeolake is situated in southern Saudi Arabia, in the Rub’ al-Khali (the ‘Empty Quarter’), the world’s largest sand desert. Here we report the first discoveries of Middle Palaeolithic and Neolithic archaeological sites in association with the palaeolake. We associate the human occupations with new geochronological data, and suggest the archaeological sites date to the wet periods of Marine Isotope Stage 5 and the Early Holocene. The archaeological sites indicate that humans repeatedly penetrated the ameliorated environments of the Rub’ al-Khali. The sites probably represent short-term occupations, with the Neolithic sites focused on hunting, as indicated by points and weaponry. Middle Palaeolithic assemblages at Mundafan support a lacustrine adaptive focus in Arabia. Provenancing of obsidian artifacts indicates that Neolithic groups at Mundafan had a wide wandering range, with transport of artifacts from distant sources. 相似文献
43.
Lalith Senarathna Nick A. Buckley Michael J. Dibley Patrick J. Kelly Shaluka F. Jayamanna Indika B. Gawarammana Andrew H. Dawson 《PloS one》2013,8(8)
Background
In developing countries, including Sri Lanka, a high proportion of acute poisoning and other medical emergencies are initially treated in rural peripheral hospitals. Patients are then usually transferred to referral hospitals for further treatment. Guidelines are often used to promote better patient care in these emergencies. We conducted a cluster randomized controlled trial (ISRCTN73983810) which aimed to assess the effect of a brief educational outreach (‘academic detailing’) intervention to promote the utilization of treatment guidelines for acute poisoning.Methods and Findings
This cluster RCT was conducted in the North Central Province of Sri Lanka. All peripheral hospitals in the province were randomized to either intervention or control. All hospitals received a copy of the guidelines. The intervention hospitals received a brief out-reach academic detailing workshop which explained poisoning treatment guidelines and guideline promotional items designed to be used in daily care. Data were collected on all patients admitted due to poisoning for 12 months post-intervention in all study hospitals. Information collected included type of poison exposure, initial investigations, treatments and hospital outcome. Patients transferred from peripheral hospitals to referral hospitals had their clinical outcomes recorded. There were 23 intervention and 23 control hospitals. There were no significant differences in the patient characteristics, such as age, gender and the poisons ingested. The intervention hospitals showed a significant improvement in administration of activated charcoal [OR 2.95 (95% CI 1.28–6.80)]. There was no difference between hospitals in use of other decontamination methods.Conclusion
This study shows that an educational intervention consisting of brief out-reach academic detailing was effective in changing treatment behavior in rural Sri Lankan hospitals. The intervention was only effective for treatments with direct clinician involvement, such as administering activated charcoal. It was not successful for treatments usually administered by non-professional staff such as forced emesis for poisoning.Trial Registration
Controlled-Trials.com ISRCTN73983810 ISRCTN73983810 相似文献44.
Eva Veronesi Frank Antony Simon Gubbins Nick Golding Alison Blackwell Peter PC. Mertens Joe Brownlie Karin E. Darpel Philip S. Mellor Simon Carpenter 《PloS one》2013,8(8)
Background
Culicoides biting midges (Diptera: Ceratopogonidae) are the biological vectors of globally significant arboviruses of livestock including bluetongue virus (BTV), African horse sickness virus (AHSV) and the recently emerging Schmallenberg virus (SBV). From 2006–2009 outbreaks of BTV in northern Europe inflicted major disruption and economic losses to farmers and several attempts were made to implicate Palaearctic Culicoides species as vectors. Results from these studies were difficult to interpret as they used semi-quantitative RT-PCR (sqPCR) assays as the major diagnostic tool, a technique that had not been validated for use in this role. In this study we validate the use of these assays by carrying out time-series detection of BTV RNA in two colony species of Culicoides and compare the results with the more traditional isolation of infectious BTV on cell culture.Methodology/Principal Findings
A BTV serotype 1 strain mixed with horse blood was fed to several hundred individuals of Culicoides sonorensis (Wirth & Jones) and C. nubeculosus (Mg.) using a membrane-based assay and replete individuals were then incubated at 25°C. At daily intervals 25 Culicoides of each species were removed from incubation, homogenised and BTV quantified in each individual using sqPCR (Cq values) and virus isolation on a KC-C. sonorensis embryonic cell line, followed by antigen enzyme-linked immunosorbent assay (ELISA). In addition, comparisons were also drawn between the results obtained with whole C. sonorensis and with individually dissected individuals to determine the level of BTV dissemination.Conclusions/Significance
Cq values generated from time-series infection experiments in both C. sonorensis and C. nubeculosus confirmed previous studies that relied upon the isolation and detection of infectious BTV. Implications on the testing of field-collected Culicoides as potential virus vectors by PCR assays and the use of such assays as front-line tools for use in diagnostic laboratories in this role are discussed. 相似文献45.
Wouter Schellekens Richard J. A. Van Wezel Natalia Petridou Nick F. Ramsey Mathijs Raemaekers 《PloS one》2013,8(6)
Recent imaging studies have reported directional motion biases in human visual cortex when perceiving moving random dot patterns. It has been hypothesized that these biases occur as a result of the integration of motion detector activation along the path of motion in visual cortex. In this study we investigate the nature of such motion integration with functional MRI (fMRI) using different motion stimuli. Three types of moving random dot stimuli were presented, showing either coherent motion, motion with spatial decorrelations or motion with temporal decorrelations. The results from the coherent motion stimulus reproduced the centripetal and centrifugal directional motion biases in V1, V2 and V3 as previously reported. The temporally decorrelated motion stimulus resulted in both centripetal and centrifugal biases similar to coherent motion. In contrast, the spatially decorrelated motion stimulus resulted in small directional motion biases that were only present in parts of visual cortex coding for higher eccentricities of the visual field. In combination with previous results, these findings indicate that biased motion responses in early visual cortical areas most likely depend on the spatial integration of a simultaneously activated motion detector chain. 相似文献
46.
Jemima L. Whyte Andrew A. Smith Bo Liu Wilfred R. Manzano Nick D. Evans Girija R. Dhamdhere Mark Y. Fang Howard Y. Chang Anthony E. Oro Jill A. Helms 《PloS one》2013,8(10)
Wnt signaling is required for both the development and homeostasis of the skin, yet its contribution to skin wound repair remains controversial. By employing Axin2LacZ/+ reporter mice we evaluated the spatial and temporal distribution patterns of Wnt responsive cells, and found that the pattern of Wnt responsiveness varies with the hair cycle, and correlates with wound healing potential. Using Axin2LacZ/LacZ mice and an ear wound model, we demonstrate that amplified Wnt signaling leads to improved healing. Utilizing a biochemical approach that mimics the amplified Wnt response of Axin2LacZ/LacZ mice, we show that topical application of liposomal Wnt3a to a non-healing wound enhances endogenous Wnt signaling, and results in better skin wound healing. Given the importance of Wnt signaling in the maintenance and repair of skin, liposomal Wnt3a may have widespread application in clinical practice. 相似文献
47.
Leroux Nicole Nouhin Janin Prak Sophearot Roth Bunthoeun Rouet François Dussart Philippe Marx Nick 《International journal of primatology》2020,41(4):634-653
International Journal of Primatology - The risk of transmitting novel pathogens from released animals to wild conspecifics is an important consideration for reintroduction initiatives. Apart from... 相似文献
48.
We benchmark the performance of four treatments of electron exchange and correlation in the prediction of structural and elastic properties of a range of minerals. The treatments used are the Hartree-Fock (HF) theory, the local density approximation (LDA) and the generalised gradient approximation (GGA) to the density functional theory (DFT) and Becke's three parameter hybrid functional (B3LYP). We find that the hybrid functional, B3LYP method yields computed elastic properties in significantly better agreement to experiment than HF or DFT-LDA and performs at least as well, if not better than the most successful DFT-GGA functionals. We suggest that B3LYP is a simple, reliable and computationally efficient tool for the ab initio simulation of mineral systems. 相似文献
49.
Nick Drydakis 《Ethnic and racial studies》2013,36(12):2054-2074
In the current study, we analyse the effect of having a Roma background on women's wages. By utilizing data from sixteen multiethnic municipalities in which Roma live, we estimate that 66.2 per cent of the wage differential between Roma and non-Roma female workers cannot be explained by differences in observed characteristics. Prejudices against Roma women are discussed and appear to explain the wage gap found here. The occupational segregation of the Roma in low-paid jobs and employers' statistical motivations are also found to influence wages earned by Roma. This study concludes that there is a need for better implementation of existing laws, rules and regulations, which would counter the discrimination against minority women in the labour market. In addition, a better means of assessing workers' skills might contribute to the reduction of wage discrimination, and greater educational achievement would significantly boost the economic status of Roma women. 相似文献
50.
Stephanie Pfaffen Raz Abdulqadir Nick E. Le Brun Michael E. P. Murphy 《The Journal of biological chemistry》2013,288(21):14917-14925
A novel ferritin was recently found in Pseudo-nitzschia multiseries (PmFTN), a marine pennate diatom that plays a major role in global primary production and carbon sequestration into the deep ocean. Crystals of recombinant PmFTN were soaked in iron and zinc solutions, and the structures were solved to 1.65–2.2-Å resolution. Three distinct iron binding sites were identified as determined from anomalous dispersion data from aerobically grown ferrous soaked crystals. Sites A and B comprise the conserved ferroxidase active site, and site C forms a pathway leading toward the central cavity where iron storage occurs. In contrast, crystal structures derived from anaerobically grown and ferrous soaked crystals revealed only one ferrous iron in the active site occupying site A. In the presence of dioxygen, zinc is observed bound to all three sites. Iron oxidation experiments using stopped-flow absorbance spectroscopy revealed an extremely rapid phase corresponding to Fe(II) oxidation at the ferroxidase site, which is saturated after adding 48 ferrous iron to apo-PmFTN (two ferrous iron per subunit), and a much slower phase due to iron core formation. These results suggest an ordered stepwise binding of ferrous iron and dioxygen to the ferroxidase site in preparation for catalysis and a partial mobilization of iron from the site following oxidation. 相似文献