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101.
Andrew P. Marsden Jeffrey J. Hollins Charles O’Neill Pavel Ryzhov Sally Higson Carolina A.T.F. Mendonça Tristan O. Kwan Lee Gyan Kwa Annette Steward Jane Clarke 《Journal of molecular biology》2018,430(24):5207-5216
Determining the relationship between protein folding pathways on and off the ribosome remains an important area of investigation in biology. Studies on isolated domains have shown that alteration of the separation of residues in a polypeptide chain, while maintaining their spatial contacts, may affect protein stability and folding pathway. Due to the vectorial emergence of the polypeptide chain from the ribosome, chain connectivity may have an important influence upon cotranslational folding. Using MATH, an all β-sandwich domain, we investigate whether the connectivity of residues and secondary structure elements is a key determinant of when cotranslational folding can occur on the ribosome. From Φ-value analysis, we show that the most structured region of the transition state for folding in MATH includes the N and C terminal strands, which are located adjacent to each other in the structure. However, arrest peptide force-profile assays show that wild-type MATH is able to fold cotranslationally, while some C-terminal residues remain sequestered in the ribosome, even when destabilized by 2–3?kcal?mol?1. We show that, while this pattern of Φ-values is retained in two circular permutants in our studies of the isolated domains, one of these permutants can fold only when fully emerged from the ribosome. We propose that in the case of MATH, onset of cotranslational folding is determined by the ability to form a sufficiently stable folding nucleus involving both β-sheets, rather than by the location of the terminal strands in the ribosome tunnel. 相似文献
102.
Tristan McCaughey Christine Y. Chen Elisabeth De Smit Gwyneth Rees Eva Fenwick Lisa S. Kearns David A. Mackey Casimir MacGregor Megan Munsie Anthony L. Cook Alice Pébay Alex W. Hewitt 《Cell and tissue banking》2016,17(3):449-456
The ability to generate human induced pluripotent stem cells (iPSCs) has opened new avenues for human disease modelling and therapy. The aim of our study was to determine research participants’ understanding of the information given when donating skin biopsies for the generation of patient-specific iPSCs. A customised 35-item questionnaire based on previous iPSC consent guidelines was sent to participants who had previously donated samples for iPSC research. The questionnaire asked pertinent demographic details, participants' motivation to take part in iPSC research and their attitudes towards related ethical issues. 234 participants were contacted with 141 (60.3 %) complete responses received. The median duration between recruitment and follow-up questioning was 313 days (range 10–573 days). The majority of participants (n = 129, 91.5 %) believed they understood what a stem cell was; however, only 22 (16.1 %) correctly answered questions related to basic stem cell properties. We found no statistically significant difference in responses from participants with different levels of education, or those with a health sciences background. The poor understanding amongst participants of iPSC research is unlikely to be unique to our study and may impact future research if not improved. As such, there is a need to develop an easily understood yet comprehensive consent process to ensure ongoing ethical progress of iPSC biobanking. 相似文献
103.
Keke Liu Yukun Guo Qisheng You Tristan Hormel Thomas S Hwang Yali Jia 《Experimental biology and medicine (Maywood, N.J.)》2021,246(20):2230
A limitation of conventional optical coherence tomography angiography (OCTA) is the limited field of view normally used in data acquisition. As the technology improves, larger fields of view that capture information away from the macular are being explored in order to provide an enhanced ability to detect pathology. However, normative measurements for important OCTA metrics like vessel density and intercapillary distance are not currently well-characterized in the peripheral retina. In this prospective study, we measured vessel density and intercapillary distance of the superficial vascular complex, ganglion cell layer plexus, and deep capillary plexus in montaged macular/temporal scans from 53 (33 men) healthy volunteers. Vessel density and intercapillary distance were also compared across different regions of the retina, including along arcs at separate distance from the fovea. Compared to the central macular region, the temporal retina had significantly lower vessel density, decreased thickness, and greater intercapillary distance in the superficial vascular complex, GCLP ganglion cell layer plexus, and deep capillary plexus (Wilcoxon rank sum test P < 0.001), with each of the plexuses examined here showing a general decrease in vessel density and an increase in intercapillary distance towards the temporal region. No significant difference was noted comparing corresponding vessel density and intercapillary distance regions above and below the macula, and multiple linear regression showed that age and intraocular pressure were not associated with vessel density and intercapillary distance in most models. Repeatability analysis reported as intraclass correlation coefficients demonstrated moderate to excellent reliability of vessel density and intercapillary distance in all OCTA layers. These results should help provide an enhanced baseline to help identify vascular pathology in the peripheral retina. 相似文献
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105.
Determinants of woody encroachment and cover in African savannas 总被引:1,自引:0,他引:1
Aisling?P.?DevineEmail author Robbie?A.?McDonald Tristan?Quaife Ilya?M.?D.?Maclean 《Oecologia》2017,183(4):939-951
Savanna ecosystems are an integral part of the African landscape and sustain the livelihoods of millions of people. Woody encroachment in savannas is a widespread phenomenon but its causes are widely debated. We review the extensive literature on woody encroachment to help improve understanding of the possible causes and to highlight where and how future scientific efforts to fully understand these causes should be focused. Rainfall is the most important determinant of maximum woody cover across Africa, but fire and herbivory interact to reduce woody cover below the maximum at many locations. We postulate that woody encroachment is most likely driven by CO2 enrichment and propose a two-system conceptual framework, whereby mechanisms of woody encroachment differ depending on whether the savanna is a wet or dry system. In dry savannas, the increased water-use efficiency in plants relaxes precipitation-driven constraints and increases woody growth. In wet savannas, the increase of carbon allocation to tree roots results in faster recovery rates after disturbance and a greater likelihood of reaching sexual maturity. Our proposed framework can be tested using a mixture of experimental and earth observational techniques. At a local level, changes in precipitation, burning regimes or herbivory could be driving woody encroachment, but are unlikely to be the explanation of this continent-wide phenomenon. 相似文献
106.
107.
Tristan Ivory 《Ethnic and racial studies》2017,40(1):172-189
This paper introduces the concept of strategic ethnic performance (SEP), when members of one ethnic group present themselves as members of a phenotypically similar ethnic group for economic gain. I use ethnographic and interview data focused on Sub-Saharan African merchants involved in the Hip Hop fashion boutique business in urban Japan to show how SEP develops from four interconnected areas: the opportunity structure for ethnic entrepreneurs, the physical presentation of sellers, the arrangement of the selling venue, and feedback loops between the seller and the consumer. By utilizing SEP, ethnic entrepreneurs enhance the perceived authenticity of their goods and themselves. A thorough analysis of this process illuminates the interactional nature of ethnic authenticity as it is understood by consumers within urban areas. 相似文献
108.
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110.
Nadine S. Taylor Ralf J. M. Weber Andrew D. Southam Tristan G. Payne Olga Hrydziuszko Theodoros N. Arvanitis Mark R. Viant 《Metabolomics : Official journal of the Metabolomic Society》2009,5(1):44-58
Currently there is a surge of interest in exploiting toxicogenomics to screen the toxicity of chemicals, enabling rapid and
accurate categorisation into classes of defined mode-of-action (MOA), and prioritising chemicals for further testing. Direct
infusion FT-ICR mass spectrometry-based metabolomics can provide a sensitive and unbiased analysis of metabolites in only
15 mins and therefore has considerable potential for chemical screening. The water flea, Daphnia magna, is an OECD test species and is utilised internationally for toxicity testing. However, no metabolomics studies of this species
have been reported. Here we optimised and evaluated the effectiveness of FT-ICR mass spectrometry metabolomics for toxicity
testing in D. magna. We confirmed that high-quality mass spectra can be recorded from as few as 30 neonates (<24 h old; 224 μg dry mass) or a
single adult daphnid (301 μg dry mass). An OECD 24 h acute toxicity test was conducted with neonates at copper concentrations
of 0, 5, 10, 25, 50 μg l−1. A total of 5447 unique peaks were detected reproducibly, of which 4768 were assigned at least one empirical formula and
1017 were putatively identified based upon accurate mass measurements. Significant copper-induced changes to the daphnid metabolome,
consistent with the documented MOA of copper, were detected thereby validating the approach. In addition, N-acetylspermidine was putatively identified as a novel biomarker of copper toxicity. Collectively, our results highlight the
excellent sensitivity, reproducibility and mass accuracy of FT-ICR mass spectrometry, and provide strong evidence for its
applicability to high-throughput screening of chemical toxicity in D. magna.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献