全文获取类型
收费全文 | 4773篇 |
免费 | 33篇 |
国内免费 | 8篇 |
出版年
2024年 | 32篇 |
2023年 | 354篇 |
2022年 | 226篇 |
2021年 | 271篇 |
2020年 | 357篇 |
2019年 | 448篇 |
2018年 | 422篇 |
2017年 | 303篇 |
2016年 | 358篇 |
2015年 | 199篇 |
2014年 | 450篇 |
2013年 | 909篇 |
2012年 | 40篇 |
2011年 | 39篇 |
2010年 | 37篇 |
2009年 | 12篇 |
2008年 | 20篇 |
2007年 | 19篇 |
2006年 | 6篇 |
2005年 | 50篇 |
2004年 | 33篇 |
2003年 | 24篇 |
2002年 | 23篇 |
2001年 | 7篇 |
2000年 | 9篇 |
1999年 | 8篇 |
1998年 | 12篇 |
1997年 | 9篇 |
1996年 | 2篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1992年 | 1篇 |
1989年 | 1篇 |
1986年 | 2篇 |
1985年 | 13篇 |
1984年 | 20篇 |
1983年 | 22篇 |
1982年 | 11篇 |
1981年 | 9篇 |
1980年 | 10篇 |
1979年 | 10篇 |
1978年 | 7篇 |
1977年 | 9篇 |
1976年 | 3篇 |
1975年 | 4篇 |
1974年 | 6篇 |
1973年 | 2篇 |
排序方式: 共有4814条查询结果,搜索用时 62 毫秒
131.
Valérie Abécassis Philippe Urban Lawrence Aggerbeck Gilles Truan Denis Pompon 《Biocatalysis and Biotransformation》2013,31(2):55-66
AbstractTwo complementary methods are described that associate in vitro and in vivo steps to generate sequence diversity by segment directed saturated mutagenesis and family shuffling. A high-throughput DNA chip-based procedure for the characterization and potentially the equalization of combinatorial libraries is also presented. Using these approaches, two combinatorial libraries of cytochrome P450 variants derived from the CYP1A subfamily were constructed and their sequence diversity characterized. The results of functional screening using high-throughput tools for the characterization of membrane P450-catalyzed activities, suggest that the 204–214 sequence segment of human CYP1A1 is not critical for polycyclic aromatic hydrocarbon recognition, as was hypothesized from previous data. Moreover, mutations in this segment do not alter the discrimination between alkoxyresorufins, which, for all tested mutants, remained similar to that of wild-type CYP1A1. In contrast, the constructed CYP1A1–CYP1A2 mosaic structures, containing multiple crossovers, exhibit a wide range of substrate preference and regioselectivity. These mosaic structures also discriminate between closely related alkoxyresorufin substrates. These results open the way to global high-throughput analysis of structure–function relationships using combinatorial libraries of enzymes together with libraries of structurally related substrates. 相似文献
132.
Insu Jeon Ji-Yong Bae Jin-Hong Park Taek-Rim Yoon Mitsugu Todo Masaaki Mawatari 《Computer methods in biomechanics and biomedical engineering》2013,16(1):103-112
To investigate the biomechanical effect of collars, finite element analyses are carried out through two hip joints that are implanted using collared and collarless stems, respectively, and an intact hip joint model. For the analyses, the sacrum, coxal bone, and the cancellous and cortical bones of a femur are modelled using finite elements based on X-ray computed tomographic images taken from a 27-year-old woman. From the results, it is found that a collar with perfect calcar contact prevents stem subsidence and decreases the proximal–lateral gap and the lateral stem tilting. Therefore, it can impart reasonable biomechanical stability for total hip arthroplasty. However, its low load transmission ability and increased stem tilting effect due to the imperfect contact between the collar and the calcar are found to be serious problems that need to be solved. Results of clinical follow-up are presented for supporting the computational results. 相似文献
133.
《Critical reviews in biochemistry and molecular biology》2013,48(3):273-288
AbstractTranslocation into the endoplasmic reticulum (ER) is the first biogenesis step for hundreds of eukaryotic secretome proteins. Over the past 30 years, groundbreaking biochemical, structural and genetic studies have delineated one conserved pathway that enables ER translocation- the signal recognition particle (SRP) pathway. However, it is clear that this is not the only pathway which can mediate ER targeting and insertion. In fact, over the past decade, several SRP-independent pathways have been uncovered, which recognize proteins that cannot engage the SRP and ensure their subsequent translocation into the ER. These SRP-independent pathways face the same challenges that the SRP pathway overcomes: chaperoning the preinserted protein while in the cytosol, targeting it rapidly to the ER surface and generating vectorial movement that inserts the protein into the ER. This review strives to summarize the various mechanisms and machineries which mediate these stages of SRP-independent translocation, as well as examine why SRP-independent translocation is utilized by the cell. This emerging understanding of the various pathways utilized by secretory proteins to insert into the ER draws light to the complexity of the translocational task, and underlines that insertion into the ER might be more varied and tailored than previously appreciated. 相似文献
134.
《Free radical research》2013,47(10):1233-1238
AbstractThe lipid peroxidation product 4-hydroxynonenal (HNE) is a biomarker of oxidative stress which is essentially involved in the pathophysiology of many diseases. The analysis of HNE is challenging because this aldehyde is extremely reactive and thus unstable. Hence, we adopted a gas chromatography–mass spectrometry (GC–MS) method based on derivatization of HNE with pentafluorobenzylhydroxylamine–HCl followed by trimethylsilylation to trimethylsilyl ethers. Ions representative for a negative ion chemical ionization mode were recorded at m/z = 152 for HNE and at m/z = 162 for the deuterated analogon (HNE-d11) as internal standard. This excellent stable and precise GC–MS method was carefully validated for HNE, and showed good linearity (r2 = 0.998), and high specificity and sensitivity. Within-day precisions were 4.4–6.1% and between-day precisions were 5.2–10.2%. Accuracies were between 99% and 104% for the whole calibration range (2.5–250 nmol/L) of HNE.To examine the versatility of this modified GC–MS method, we analyzed HNE in ethylenediaminetetraacetic acid (EDTA) plasma in a well-defined collective of migraine patients; recently published. The results underline our former observations that women with migraine are afflicted with increased levels of HNE. Patients with thyroidal dysfunction showed no significant HNE alterations. This was confirmed by normal HNE EDTA plasma levels in hyper- und hypothyroid Sprague-Dawley rats.Taken together, the GC–MS method presented herein is of excellent quality to record oxidative stress-related bioactive HNE levels. This is important for a reorientation of oxidative stress analytics in other human diseases first of atherosclerosis and cancer. 相似文献
135.
Hale Z. Toklu Tayfun Hakan Necat Bi˙ber Seyhun Solakoğlu Ayli˙z Velioğlu Öğünç 《Free radical research》2013,47(7):658-667
Traumatic brain injury (TBI) was induced by a weight-drop device using 300 g–1 m weight-height impact. The study groups were: control, alpha-lipoic acid (LA) (100 mg/kg, po), TBI, and TBI + LA (100 mg/kg, po). Forty-eight hours after the injury, neurological scores were measured and brain samples were taken for histological examination or determination of thiobarbituric acid reactive substances (TBARS) and glutathione (GSH) levels, myeloperoxidase (MPO) and Na+-K+ ATPase activities, whereas cytokines (TNF-α, IL-1β) were determined in blood. Brain oedema was evaluated by wet–dry weight method and blood–brain barrier (BBB) permeability was evaluated by Evans Blue (EB) extravasation. As a result, neurological scores mildly increased in trauma groups. Moreover, TBI caused a significant decrease in brain GSH and Na+-K+ ATPase activity, which was accompanied with significant increases in TBARS level, MPO activity and plasma proinflammatory cytokines. LA treatment reversed all these biochemical indices as well as histopathological alterations. TBI also caused a significant increase in brain water content and EB extravasation which were partially reversed by LA treatment. These findings suggest that LA exerts neuroprotection by preserving BBB permeability and by reducing brain oedema probably by its anti-inflammatory and antioxidant properties in the TBI model. 相似文献
136.
《Free radical research》2013,47(4):285-286
The purpose of this review is to bring together the different approaches for studying the oxidation of low density lipoproteins and try to identify some critical factors which will permit greater comparability between laboratories. These issues are discussed both in terms of the variety of exogenous mediators of oxidation applied (transition metal ions, haem proteins, azo initiators, peroxynitrite, cells etc.) and their raisons d'etre, as well as the methodologies (formation of conjugated dienes, hydroperoxides, decomposition products of lipid peroxidation, altered surface charge, macrophage uptake) applicable to the different stages of the oxidation and the factors underlying their accurate execution and interpretation. 相似文献
137.
Elisabetta Damiani Riccardo Castagna Paola Astolfi Lucedio Greci 《Free radical research》2013,47(3):325-336
Nitroxide radicals are an emerging class of interesting compounds with versatile antioxidant and radioprotective properties. All literature studies have so far concentrated on compounds bearing only one nitroxide function. Here, we now investigate and compare the radical scavenging behaviour and antioxidant activity of aromatic indolinonic and aliphatic piperidine bis-nitroxides, i.e compounds bearing two nitroxide functions. Their corresponding mono-derivatives were also studied for comparison. Radical scavenging activity was investigated using EPR and UV–Vis spectroscopy by following spectral changes in acetonitrile of the nitroxides in the presence of alkyl and peroxyl radicals generated, respectively, under anoxic or aerobic conditions from thermal decomposition of AMVN [2,2′-azobis(2,4-di-methylvaleronitrile)]. Antioxidant activity of the nitroxides was evaluated by monitoring conjugated dienes (CD) formation during methyl linoleate micelles peroxidation and by measuring carbonyl content in oxidized bovine serum albumin (BSA). The results show that: (a) each nitroxide moiety in bis-nitroxides scavenges radicals independent of each other; (b) aliphatic nitroxides do not scavenge peroxyl radicals, at least under the experimental conditions used here, whereas indolinonic aromatic ones do: their stoichiometric number is 1.14 and 2.17, respectively, for mono- and bis-derivatives; (c) bis-nitroxides are roughly twice more efficient at inhibiting lipid peroxidation compared to their corresponding mono-derivatives. Although this study provides only comparative information on the relative radical-scavenging abilities of mono- and bis-nitroxides, it helps in understanding further the interesting reactivity of these compounds especially with regards to peroxyl radicals where many controversies in the literature exist. 相似文献
138.
Gretchen M. Reevy 《Journal of applied animal welfare science : JAAWS》2013,16(3):239-258
Few studies have examined how personality traits may be related to the amounts and types of attachments humans have toward companion animals (pets). In this study, 1,098 companion animal guardians (owners) completed a survey that included the Big Five Inventory, the Lexington Attachment to Pets Scale, and the Pet Attachment Questionnaire. Each participant chose whether he or she identified as a Cat Person, Dog Person, Both, or Neither. Results indicated that neuroticism, conscientiousness, choosing a dog as a favorite pet, and identifying as a Cat Person, Dog Person, or Both predicted affection for a pet. Conscientiousness, extraversion, and openness decreased avoidant attachment to pets, and neuroticism increased anxious attachment to pets. Both dogs and cats could benefit from pet owners who are conscientious, and there may be some benefits of neuroticism in pet owners. The findings of this study will advance understanding of the human–animal bond. As this understanding increases, measurements of human attachment and personality may be useful for the development of tools that could assist shelter employees and veterinarians in counseling people about pet ownership. 相似文献
139.
Abstract In recent years, Laser Microdissection (LM), which has been widely used in animal biology, has been adapted to plant tissues. This short paper focuses on some technical aspects concerning plant sample preparation for LM technology, with particular attention to the application of gene expression and proteomics studies. Examples derived from the use of different LM methods are reported and their applications to plant–microbe interactions are explored. 相似文献
140.
Alexej V. Sokolov Kira V. Ageeva Maria O. Pulina Olga S. Cherkalina Valeria R. Samygina Irina I. Vlasova 《Free radical research》2013,47(11-12):989-998
Ceruloplasmin (CP), the multicopper oxidase of plasma, interacts with myeloperoxidase (MPO), an enzyme of leukocytes, and inhibits its peroxidase and chlorinating activity. Studies on the enzymatic properties shows that CP behaves as a competitive inhibitor impeding the binding of aromatic substrates to the active centre of MPO. The contact between CP and MPO probably entails conformational changes close to the p-phenylenediamine binding site in CP, which explains the observed activation by MPO of the substrate's oxidation. CP subjected to partial proteolysis was virtually unable to inhibit activity of MPO. The possible protein–protein interface is comprised of the area near active site of MPO and the loop linking domains 5 and 6 in CP. One of the outcomes of this study is the finding of a new link between antioxidant properties of CP and its susceptibility to proteolysis. 相似文献