全文获取类型
收费全文 | 3750篇 |
免费 | 304篇 |
国内免费 | 1篇 |
专业分类
4055篇 |
出版年
2024年 | 4篇 |
2023年 | 25篇 |
2022年 | 65篇 |
2021年 | 115篇 |
2020年 | 63篇 |
2019年 | 86篇 |
2018年 | 87篇 |
2017年 | 78篇 |
2016年 | 153篇 |
2015年 | 214篇 |
2014年 | 220篇 |
2013年 | 313篇 |
2012年 | 310篇 |
2011年 | 310篇 |
2010年 | 191篇 |
2009年 | 147篇 |
2008年 | 246篇 |
2007年 | 232篇 |
2006年 | 238篇 |
2005年 | 178篇 |
2004年 | 174篇 |
2003年 | 136篇 |
2002年 | 113篇 |
2001年 | 36篇 |
2000年 | 33篇 |
1999年 | 27篇 |
1998年 | 30篇 |
1997年 | 21篇 |
1996年 | 15篇 |
1995年 | 20篇 |
1994年 | 20篇 |
1993年 | 16篇 |
1992年 | 8篇 |
1991年 | 20篇 |
1990年 | 12篇 |
1989年 | 10篇 |
1988年 | 11篇 |
1987年 | 4篇 |
1986年 | 4篇 |
1985年 | 8篇 |
1983年 | 5篇 |
1981年 | 4篇 |
1978年 | 3篇 |
1976年 | 4篇 |
1974年 | 4篇 |
1973年 | 3篇 |
1969年 | 4篇 |
1967年 | 5篇 |
1966年 | 3篇 |
1949年 | 4篇 |
排序方式: 共有4055条查询结果,搜索用时 0 毫秒
121.
Kerstin Delius Martina Günderoth‐Palmowski Ina Krause Wolfgang Engelmann 《Biological Rhythm Research》2013,44(4):289-299
Abstract LiCl (195 μg/g body weight and day) reduces water uptake in Syrian hamsters by 40%. Sleep duration is increased from 50% per day to 60% per day. Other behavioural items are hardly influenced. Shortening and lengthening of the circadian period was induced by Li+ in individual hamsters, but the mean period of the population was not changed. The upper limit of entrainment is increased by Li+. 相似文献
122.
Michele Tinti Lars Kiemer Stefano Costa Martin L. Miller Francesca Sacco Jesper V. Olsen Martina Carducci Serena Paoluzi Francesca Langone Christopher T. Workman Nikolaj Blom Kazuya Machida Christopher M. Thompson Mike Schutkowski Søren Brunak Matthias Mann Bruce J. Mayer Luisa Castagnoli Gianni Cesareni 《Cell reports》2013,3(4):1293-1305
Highlights? The recognition specificity of 70 SH2 domains is probed ? Recognition specificity diverges faster than sequence ? PepspotDB is a database of protein interactions mediated by SH2 domains 相似文献
123.
Christopher J Gobler Alexei V Lobanov Ying-Zhong Tang Anton A Turanov Yan Zhang Martina Doblin Gordon T Taylor Sergio A Sa?udo-Wilhelmy Igor V Grigoriev Vadim N Gladyshev 《The ISME journal》2013,7(7):1333-1343
The trace element selenium (Se) is required for the biosynthesis of selenocysteine (Sec), the 21st amino acid in the genetic code, but its role in the ecology of harmful algal blooms (HABs) is unknown. Here, we examined the role of Se in the biology and ecology of the harmful pelagophyte, Aureococcus anophagefferens, through cell culture, genomic analyses, and ecosystem studies. This organism has the largest and the most diverse selenoproteome identified to date that consists of at least 59 selenoproteins, including known eukaryotic selenoproteins, selenoproteins previously only detected in bacteria, and novel selenoproteins. The A. anophagefferens selenoproteome was dominated by the thioredoxin fold proteins and oxidoreductase functions were assigned to the majority of detected selenoproteins. Insertion of Sec in these proteins was supported by a unique Sec insertion sequence. Se was required for the growth of A. anophagefferens as cultures grew maximally at nanomolar Se concentrations. In a coastal ecosystem, dissolved Se concentrations were elevated before and after A. anophagefferens blooms, but were reduced by >95% during the peak of blooms to 0.05 nℳ. Consistent with this pattern, enrichment of seawater with selenite before and after a bloom did not affect the growth of A. anophagefferens, but enrichment during the peak of the bloom significantly increased population growth rates. These findings demonstrate that Se inventories, which can be anthropogenically enriched, can support proliferation of HABs, such as A. anophagefferens through its synthesis of a large arsenal of Se-dependent oxidoreductases that fine-tune cellular redox homeostasis. 相似文献
124.
Paula A. J. Rosa Dr. Ana M. Azevedo S. Sommerfeld Martina Mutter Werner Bäcker Prof. M. Raquel Aires-Barros 《Biotechnology journal》2013,8(3):352-362
An aqueous two-phase extraction (ATPE) process based on a PEG/phosphate system was developed for the capture of human immunoglobulin G and successfully applied to a Chinese hamster ovary and a PER.C6® cell supernatant. A continuous ATPE process incorporating three different steps (extraction, back-extraction, and washing) was set up and validated in a pump mixer-settler battery. Most of the higher molecular weight cell supernatant impurities were removed during the extraction step, while most of the lower molecular weight impurities were removed during the subsequent steps. A global recovery yield of 80% and a final protein purity of more than 99% were obtained for the IgG purification from a CHO cell supernatant, representing a 155-fold reduction in the protein/IgG ratio. For the purification of IgG from a PER.C6® cell supernatant, a global recovery yield of 100%, and a host cell protein purity were attained, representing a 22-fold reduction in the host cell protein/IgG ratio. These results, thus, open promising perspectives for the application of the developed ATPE process as a platform for the capture of antibodies. In fact, this new process has shown the ability to successfully recover and purify different antibodies from distinct cell culture supernatants. This technology can also overcome some of the limitations encountered using the typical chromatographic processes, besides inherent advantages of scalability, process integration, capability of continuous operation, and economic feasibility. 相似文献
125.
Nicholas S. Kirkby Anne K. Zaiss Paula Urquhart Jing Jiao Philip J. Austin Malak Al-Yamani Martina H. Lundberg Louise S. MacKenzie Timothy D. Warner Anna Nicolaou Harvey R. Herschman Jane A. Mitchell 《PloS one》2013,8(7)
There are two schools of thought regarding the cyclooxygenase (COX) isoform
active in the vasculature. Using urinary prostacyclin markers some groups have
proposed that vascular COX-2 drives prostacyclin release. In contrast, we and
others have found that COX-1, not COX-2, is responsible for vascular
prostacyclin production. Our experiments have relied on immunoassays to detect
the prostacyclin breakdown product, 6-keto-PGF1α and antibodies to
detect COX-2 protein. Whilst these are standard approaches, used by many
laboratories, antibody-based techniques are inherently indirect and have been
criticized as limiting the conclusions that can be drawn. To address this
question, we measured production of prostanoids, including
6-keto-PGF1α, by isolated vessels and in the circulation
in vivo using liquid chromatography tandem mass
spectrometry and found values essentially identical to those obtained by
immunoassay. In addition, we determined expression from the
Cox2 gene using a knockin reporter mouse in which
luciferase activity reflects Cox2 gene expression. Using this
we confirm the aorta to be essentially devoid of Cox2 driven
expression. In contrast, thymus, renal medulla, and regions of the brain and gut
expressed substantial levels of luciferase activity, which correlated well with
COX-2-dependent prostanoid production. These data are consistent with the
conclusion that COX-1 drives vascular prostacyclin release and puts the sparse
expression of Cox2 in the vasculature in the context of the
rest of the body. In doing so, we have identified the thymus, gut, brain and
other tissues as target organs for consideration in developing a new
understanding of how COX-2 protects the cardiovascular system. 相似文献
126.
Elham Khanicheh Martina Mitterhuber Lifen Xu Stéphanie P. Haeuselmann Gabriela M. Kuster Beat A. Kaufmann 《PloS one》2013,8(3)
Background/Objectives
Inflammatory changes on the endothelium are responsible for leukocyte recruitment to plaques in atherosclerosis. Noninvasive assessment of treatment-effects on endothelial inflammation may be of use for managing medical therapy and developing novel therapies. We hypothesized that molecular imaging of vascular cell adhesion molecule-1 (VCAM-1) with contrast enhanced ultrasound (CEU) could assess treatment effects on endothelial phenotype in early atherosclerosis.Methods
Mice with atherosclerosis produced by gene deletion of the LDL-receptor and Apobec-1-editing protein were studied. At 12 weeks of age, mice received 8 weeks of regular chow or atorvastatin-enriched chow (10 mg/kg/day). At 20 weeks, CEU molecular imaging for aortic endothelial VCAM-1 expression was performed with VCAM-1-targeted (MBVCAM) and control microbubbles (MBCtr). Aortic wall thickness was assessed with high frequency ultrasound. Histology, immunohistology and Western blot were used to assess plaque burden and VCAM-1 expression.Results
Plaque burden was reduced on histology, and VCAM-1 was reduced on Western blot by atorvastatin, which corresponded to less endothelial expression of VCAM-1 on immunohistology. High frequency ultrasound did not detect differences in aortic wall thickness between groups. In contrast, CEU molecular imaging demonstrated selective signal enhancement for MBVCAM in non-treated animals (MBVCAM 2±0.3 vs MBCtr 0.7±0.2, p<0.01), but not in statin-treated animals (MBVCAM 0.8±0.2 vs MBCtr 1.0±0.2, p = ns; p<0.01 for the effect of statin on MBVCAM signal).Conclusions
Non-invasive CEU molecular imaging detects the effects of anti-inflammatory treatment on endothelial inflammation in early atherosclerosis. This easily accessible, low-cost technique may be useful in assessing treatment effects in preclinical research and in patients. 相似文献127.
Silvia Ghirotto Francesca Tassi Erica Fumagalli Vincenza Colonna Anna Sandionigi Martina Lari Stefania Vai Emmanuele Petiti Giorgio Corti Ermanno Rizzi Gianluca De Bellis David Caramelli Guido Barbujani 《PloS one》2013,8(2)
The Etruscan culture is documented in Etruria, Central Italy, from the 8th to the 1st century BC. For more than 2,000 years there has been disagreement on the Etruscans’ biological origins, whether local or in Anatolia. Genetic affinities with both Tuscan and Anatolian populations have been reported, but so far all attempts have failed to fit the Etruscans’ and modern populations in the same genealogy. We extracted and typed the hypervariable region of mitochondrial DNA of 14 individuals buried in two Etruscan necropoleis, analyzing them along with other Etruscan and Medieval samples, and 4,910 contemporary individuals from the Mediterranean basin. Comparing ancient (30 Etruscans, 27 Medieval individuals) and modern DNA sequences (370 Tuscans), with the results of millions of computer simulations, we show that the Etruscans can be considered ancestral, with a high degree of confidence, to the current inhabitants of Casentino and Volterra, but not to the general contemporary population of the former Etruscan homeland. By further considering two Anatolian samples (35 and 123 individuals) we could estimate that the genetic links between Tuscany and Anatolia date back to at least 5,000 years ago, strongly suggesting that the Etruscan culture developed locally, and not as an immediate consequence of immigration from the Eastern Mediterranean shores. 相似文献
128.
Vincenzo Verdoliva Cinzia Senatore Maria Letizia Polci Stefania Rossi Martina Cordella Giuseppe Carlucci Paolo Marchetti Giancarlo Antonini-Cappellini Antonio Facchiano Daniela D'Arcangelo Francesco Facchiano 《PloS one》2013,8(3)
Recently developed proteomic technologies allow to profile thousands of proteins within a high-throughput approach towards biomarker discovery, although results are not as satisfactory as expected. In the present study we demonstrate that serum proteome denaturation is a key underestimated feature; in fact, a new differential denaturation protocol better discriminates serum proteins according to their electrophoretic mobility as compared to single-denaturation protocols. Sixty nine different denaturation treatments were tested and the 3 most discriminating ones were selected (TRIDENT analysis) and applied to human sera, showing a significant improvement of serum protein discrimination as confirmed by MALDI-TOF/MS and LC-MS/MS identification, depending on the type of denaturation applied. Thereafter sera from mice and patients carrying cutaneous melanoma were analyzed through TRIDENT. Nine and 8 protein bands were found differentially expressed in mice and human melanoma sera, compared to healthy controls (p<0.05); three of them were found, for the first time, significantly modulated: α2macroglobulin (down-regulated in melanoma, p<0.001), Apolipoprotein-E and Apolipoprotein-A1 (both up-regulated in melanoma, p<0.04), both in mice and humans. The modulation was confirmed by immunological methods. Other less abundant proteins (e.g. gelsolin) were found significantly modulated (p<0.05).Conclusions: i) serum proteome contains a large amount of information, still neglected, related to proteins folding; ii) a careful serum denaturation may significantly improve analytical procedures involving complex protein mixtures; iii) serum differential denaturation protocol highlights interesting proteomic differences between cancer and healthy sera. 相似文献
129.
Lisa Gruber Sigrid Kisling Pia Lichti Fran?ois-Pierre Martin Stephanie May Martin Klingenspor Martina Lichtenegger Michael Rychlik Dirk Haller 《PloS one》2013,8(8)
Background
Obesity has been associated with a more severe disease course in inflammatory bowel disease (IBD) and epidemiological data identified dietary fats but not obesity as risk factors for the development of IBD. Crohn’s disease is one of the two major IBD phenotypes and mostly affects the terminal ileum. Despite recent observations that high fat diets (HFD) impair intestinal barrier functions and drive pathobiont selection relevant for chronic inflammation in the colon, mechanisms of high fat diets in the pathogenesis of Crohn’s disease are not known. The aim of this study was to characterize the effect of HFD on the development of chronic ileal inflammation in a murine model of Crohn’s disease-like ileitis.Methods
TNFΔARE/WT mice and wildtype C57BL/6 littermates were fed a HFD compared to control diet for different durations. Intestinal pathology and metabolic parameters (glucose tolerance, mesenteric tissue characteristics) were assessed. Intestinal barrier integrity was characterized at different levels including polyethylene glycol (PEG) translocation, endotoxin in portal vein plasma and cellular markers of barrier function. Inflammatory activation of epithelial cells as well as immune cell infiltration into ileal tissue were determined and related to luminal factors.Results
HFD aggravated ileal inflammation but did not induce significant overweight or typical metabolic disorders in TNFΔARE/WT. Expression of the tight junction protein Occludin was markedly reduced in the ileal epithelium of HFD mice independently of inflammation, and translocation of endotoxin was increased. Epithelial cells showed enhanced expression of inflammation-related activation markers, along with enhanced luminal factors-driven recruitment of dendritic cells and Th17-biased lymphocyte infiltration into the lamina propria.Conclusions
HFD feeding, independently of obesity, accelerated disease onset of small intestinal inflammation in Crohn’s disease-relevant mouse model through mechanisms that involve increased intestinal permeability and altered luminal factors, leading to enhanced dendritic cell recruitment and promoted Th17 immune responses. 相似文献130.
Rachael Miller Kate L. Laskowski Martina Schiestl Thomas Bugnyar Christine Schwab 《PloS one》2016,11(2)
Consistent individual differences in behaviour, or ‘personality’, are likely to be influenced by development, social context, and species ecology, though few comparative, longitudinal studies exist. Here, we investigated the role of development and social context on personality variation in two identically reared, social corvids: common ravens and carrion crows. We repeatedly presented subjects with a variety of novel food and objects, while alone and in a primarily sibling subgroup, from fledging to sub-adulthood. We predicted that consistent individual differences would emerge later in development, and that conspecific presence would facilitate behavioural similarities. In contrast to our predictions, we found that individuals of both species were highly inconsistent in their behavioural responses throughout the development period. In line with our predictions, though in the ravens only, conspecific presence promoted behavioural similarities as individuals were strongly shaped by their subgroup, and it is likely that these effects were driven by social context rather than relatedness. We discuss these findings in relation to developmental steps and the role of social relations in these species. Overall, our findings highlight that these two species are highly adaptable in their behaviour, and the ravens in particular are strongly influenced by their social environment, which may facilitate cooperation and social learning. 相似文献