全文获取类型
收费全文 | 2413篇 |
免费 | 244篇 |
出版年
2021年 | 24篇 |
2019年 | 18篇 |
2018年 | 26篇 |
2017年 | 18篇 |
2016年 | 38篇 |
2015年 | 71篇 |
2014年 | 86篇 |
2013年 | 79篇 |
2012年 | 80篇 |
2011年 | 86篇 |
2010年 | 72篇 |
2009年 | 55篇 |
2008年 | 81篇 |
2007年 | 84篇 |
2006年 | 88篇 |
2005年 | 69篇 |
2004年 | 74篇 |
2003年 | 68篇 |
2002年 | 65篇 |
2001年 | 52篇 |
2000年 | 58篇 |
1999年 | 45篇 |
1998年 | 28篇 |
1997年 | 18篇 |
1996年 | 25篇 |
1995年 | 26篇 |
1993年 | 20篇 |
1992年 | 29篇 |
1991年 | 36篇 |
1990年 | 41篇 |
1989年 | 43篇 |
1988年 | 43篇 |
1987年 | 40篇 |
1986年 | 45篇 |
1985年 | 45篇 |
1984年 | 35篇 |
1983年 | 33篇 |
1982年 | 18篇 |
1981年 | 32篇 |
1980年 | 24篇 |
1979年 | 36篇 |
1978年 | 21篇 |
1976年 | 18篇 |
1975年 | 21篇 |
1974年 | 30篇 |
1973年 | 29篇 |
1972年 | 21篇 |
1969年 | 19篇 |
1967年 | 25篇 |
1966年 | 19篇 |
排序方式: 共有2657条查询结果,搜索用时 78 毫秒
191.
192.
Role of UEV-1, an Inactive Variant of the E2 UbiquitinConjugating Enzymes, in In Vitro Differentiation and Cell Cycle Behavior of HT-29-M6 Intestinal Mucosecretory Cells 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
193.
Isopods are one of the key marine groups that radiated extensively in the southern high-latitude regions, and it is widely assumed that they did so essentially through the Cenozoic era. Nevertheless, palaeontological evidence is now beginning to accumulate which suggests that some at least of the key isopod taxa may be of considerably greater antiquity. In particular, Schweglerella strobli Polz from the Early Tithonian Plattenkalk of Solnhofen, southern Germany indicates that the suborder Sphaeromatidea is of at least Late Jurassic ancestry, and possibly much older. Schweglerella strobli is phylogenetically close to both the Bathynataliidae and Serolidae, but is here placed in a new family, Schweglerellidae. Like the decapods, the early phylogenetic history of the isopods may be characterized by a considerable macroevolutionary lag. Perhaps a number of major marine invertebrate groups underwent a Mesozoic phase of widespread dispersal when the Pangaean margins were still largely intact and climates globally more equable? The subsequent radiation of groups such as the sphaeromatidean isopods may have been largely contingent upon the Cenozoic thermal isolation of the Southern Ocean. 相似文献
194.
195.
Willize E. van der Starre Cees van Nieuwkoop Uginia Thomson Marleen S. M. Zijderveld-Voshart Jan Pieter R. Koopman Tanny J. K. van der Reijden Jaap T. van Dissel Esther van de Vosse 《PloS one》2015,10(3)
Objective/Purpose
Febrile urinary tract infection (UTI) is a common bacterial disease that may lead to substantial morbidity and mortality especially among the elderly. Little is known about biomarkers that predict a complicated course. Our aim was to determine the role of certain urinary cytokines or antimicrobial proteins, plasma vitamin D level, and genetic variation in host defense of febrile UTI and its relation with bacteremia.Methods
A case-control study. Out of a cohort of consecutive adults with febrile UTI (n = 787) included in a multi-center observational cohort study, 46 cases with bacteremic E.coli UTI and 45 cases with non-bacteremic E.coli UTI were randomly selected and compared to 46 controls. Urinary IL-6, IL-8, LL37, β-defensin 2 and uromodulin as well as plasma 25-hydroxyvitamin D were measured. In 440 controls and 707 UTI patients polymorphisms were genotyped in the genes CXCR1, DEFA4, DEFB1, IL6, IL8, MYD88, UMOD, TIRAP, TLR1, TLR2, TLR5 and TNF.Results
IL-6, IL-8, and LL37 are different between controls and UTI patients, although these proteins do not distinguish between patients with and without bacteremia. While uromodulin did not differ between groups, inability to produce uromodulin is more common in patients with bacteremia. Most participants in the study, including the controls, had insufficient vitamin D and, at least in winter, UTI patients have lower vitamin D than controls. Associations were found between the CC genotype of IL6 SNP rs1800795 and occurrence of bacteremia and between TLR5 SNP rs5744168 and protection from UTI. The rare GG genotype of IL6 SNP rs1800795 was associated with higher β-defensin 2 production.Conclusion
Although no biomarker was able to distinguish between UTI with or without bacteremia, two risk factors for bacteremia were identified. These were inability to produce uromodulin and an IL6 rs1800795 genotype. 相似文献196.
Malcolm R. Macleod Aaron Lawson McLean Aikaterini Kyriakopoulou Stylianos Serghiou Arno de Wilde Nicki Sherratt Theo Hirst Rachel Hemblade Zsanett Bahor Cristina Nunes-Fonseca Aparna Potluru Andrew Thomson Julija Baginskitae Kieren Egan Hanna Vesterinen Gillian L. Currie Leonid Churilov David W. Howells Emily S. Sena 《PLoS biology》2015,13(10)
197.
Mariaelena Caboni Thierry Pédron Omar Rossi David Goulding Derek Pickard Francesco Citiulo Calman A. MacLennan Gordon Dougan Nicholas R. Thomson Allan Saul Philippe J. Sansonetti Christiane Gerke 《PLoS pathogens》2015,11(3)
Shigella is the leading cause for dysentery worldwide. Together with several virulence factors employed for invasion, the presence and length of the O antigen (OAg) of the lipopolysaccharide (LPS) plays a key role in pathogenesis. S. flexneri 2a has a bimodal OAg chain length distribution regulated in a growth-dependent manner, whereas S. sonnei LPS comprises a monomodal OAg. Here we reveal that S. sonnei, but not S. flexneri 2a, possesses a high molecular weight, immunogenic group 4 capsule, characterized by structural similarity to LPS OAg. We found that a galU mutant of S. sonnei, that is unable to produce a complete LPS with OAg attached, can still assemble OAg material on the cell surface, but a galU mutant of S. flexneri 2a cannot. High molecular weight material not linked to the LPS was purified from S. sonnei and confirmed by NMR to contain the specific sugars of the S. sonnei OAg. Deletion of genes homologous to the group 4 capsule synthesis cluster, previously described in Escherichia coli, abolished the generation of the high molecular weight OAg material. This OAg capsule strongly affects the virulence of S. sonnei. Uncapsulated knockout bacteria were highly invasive in vitro and strongly inflammatory in the rabbit intestine. But, the lack of capsule reduced the ability of S. sonnei to resist complement-mediated killing and to spread from the gut to peripheral organs. In contrast, overexpression of the capsule decreased invasiveness in vitro and inflammation in vivo compared to the wild type. In conclusion, the data indicate that in S. sonnei expression of the capsule modulates bacterial pathogenesis resulting in balanced capabilities to invade and persist in the host environment. 相似文献
198.
Clare L. Adam Patricia A. Williams Karen E. Garden Lynn M. Thomson Alexander W. Ross 《PloS one》2015,10(1)
Soluble fermentable dietary fibre elicits gut adaptations, increases satiety and potentially offers a natural sustainable means of body weight regulation. Here we aimed to quantify physiological responses to graded intakes of a specific dietary fibre (pectin) in an animal model. Four isocaloric semi-purified diets containing 0, 3.3%, 6.7% or 10% w/w apple pectin were offered ad libitum for 8 or 28 days to young adult male rats (n = 8/group). Measurements were made of voluntary food intake, body weight, initial and final body composition by magnetic resonance imaging, final gut regional weights and histology, and final plasma satiety hormone concentrations. In both 8- and 28-day cohorts, dietary pectin inclusion rate was negatively correlated with food intake, body weight gain and the change in body fat mass, with no effect on lean mass gain. In both cohorts, pectin had no effect on stomach weight but pectin inclusion rate was positively correlated with weights and lengths of small intestine and caecum, jejunum villus height and crypt depth, ileum crypt depth, and plasma total glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) concentrations, and at 8 days was correlated with weight and length of colon and with caecal mucosal depth. Therefore, the gut’s morphological and endocrine adaptations were dose-dependent, occurred within 8 days and were largely sustained for 28 days during continued dietary intervention. Increasing amounts of the soluble fermentable fibre pectin in the diet proportionately decreased food intake, body weight gain and body fat content, associated with proportionately increased satiety hormones GLP-1 and PYY and intestinal hypertrophy, supporting a role for soluble dietary fibre-induced satiety in healthy body weight regulation. 相似文献
199.
Ana Maria Fernandez-Pujals Mark James Adams Pippa Thomson Andrew G. McKechanie Douglas H. R. Blackwood Blair H. Smith Anna F. Dominiczak Andrew D. Morris Keith Matthews Archie Campbell Pamela Linksted Chris S. Haley Ian J. Deary David J. Porteous Donald J. MacIntyre Andrew M. McIntosh 《PloS one》2015,10(11)
The heritability of Major Depressive Disorder (MDD) has been estimated at 37% based largely on twin studies that rely on contested assumptions. More recently, the heritability of MDD has been estimated on large populations from registries such as the Swedish, Finnish, and Chinese cohorts. Family-based designs utilise a number of different relationships and provide an alternative means of estimating heritability. Generation Scotland: Scottish Family Health Study (GS:SFHS) is a large (n = 20,198), family-based population study designed to identify the genetic determinants of common diseases, including Major Depressive Disorder. Two thousand seven hundred and six individuals were SCID diagnosed with MDD, 13.5% of the cohort, from which we inferred a population prevalence of 12.2% (95% credible interval: 11.4% to 13.1%). Increased risk of MDD was associated with being female, unemployed due to a disability, current smokers, former drinkers, and living in areas of greater social deprivation. The heritability of MDD in GS:SFHS was between 28% and 44%, estimated from a pedigree model. The genetic correlation of MDD between sexes, age of onset, and illness course were examined and showed strong genetic correlations. The genetic correlation between males and females with MDD was 0.75 (0.43 to 0.99); between earlier (≤ age 40) and later (> age 40) onset was 0.85 (0.66 to 0.98); and between single and recurrent episodic illness course was 0.87 (0.72 to 0.98). We found that the heritability of recurrent MDD illness course was significantly greater than the heritability of single MDD illness course. The study confirms a moderate genetic contribution to depression, with a small contribution of the common family environment (variance proportion = 0.07, CI: 0.01 to 0.15), and supports the relationship of MDD with previously identified risk factors. This study did not find robust support for genetic differences in MDD due to sex, age of onset, or illness course. However, we found an intriguing difference in heritability between recurrent and single MDD illness course. These findings establish GS:SFHS as a valuable cohort for the genetic investigation of MDD. 相似文献
200.
Sally Lindsay Laura R. Hartman Nick Reed Caron Gan Nicole Thomson Beverely Solomon 《PloS one》2015,10(4)