全文获取类型
收费全文 | 1180篇 |
免费 | 80篇 |
专业分类
1260篇 |
出版年
2023年 | 4篇 |
2022年 | 9篇 |
2021年 | 16篇 |
2020年 | 6篇 |
2019年 | 23篇 |
2018年 | 27篇 |
2017年 | 17篇 |
2016年 | 37篇 |
2015年 | 77篇 |
2014年 | 50篇 |
2013年 | 97篇 |
2012年 | 104篇 |
2011年 | 76篇 |
2010年 | 77篇 |
2009年 | 56篇 |
2008年 | 70篇 |
2007年 | 60篇 |
2006年 | 86篇 |
2005年 | 55篇 |
2004年 | 67篇 |
2003年 | 47篇 |
2002年 | 51篇 |
2001年 | 16篇 |
2000年 | 18篇 |
1999年 | 6篇 |
1998年 | 15篇 |
1997年 | 11篇 |
1996年 | 7篇 |
1995年 | 12篇 |
1994年 | 13篇 |
1993年 | 9篇 |
1992年 | 8篇 |
1991年 | 8篇 |
1990年 | 5篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1987年 | 5篇 |
1986年 | 3篇 |
1985年 | 3篇 |
1983年 | 1篇 |
1981年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1952年 | 1篇 |
排序方式: 共有1260条查询结果,搜索用时 15 毫秒
101.
102.
Laurence Goffin Queralt Seguin-Estévez Montserrat Alvarez Walter Reith Carlo Chizzolini 《Arthritis research & therapy》2010,12(2):R73
Introduction
Extracellular matrix (ECM) turnover is controlled by the synthetic rate of matrix proteins, including type I collagen, and their enzymatic degradation by matrix metalloproteinases (MMPs). Fibrosis is characterized by an unbalanced accumulation of ECM leading to organ dysfunction as observed in systemic sclerosis. We previously reported that proteasome inhibition (PI) in vitro decreases type I collagen and enhances MMP-1 production by human fibroblasts, thus favoring an antifibrotic fibroblast phenotype. These effects were dominant over the pro-fibrotic phenotype induced by transforming growth factor (TGF)-β. Here we investigate the molecular events responsible for the anti-fibrotic phenotype induced in fibroblasts by the proteasome inhibitor bortezomib. 相似文献103.
104.
105.
106.
José M. Pastor Vicente Bernal Manuel Salvador Montserrat Argando?a Carmen Vargas Laszlo Csonka ángel Sevilla José L. Iborra Joaquín J. Nieto Manuel Cánovas 《The Journal of biological chemistry》2013,288(24):17769-17781
Bacterial osmoadaptation involves the cytoplasmic accumulation of compatible solutes to counteract extracellular osmolarity. The halophilic and highly halotolerant bacterium Chromohalobacter salexigens is able to grow up to 3 m NaCl in a minimal medium due to the de novo synthesis of ectoines. This is an osmoregulated pathway that burdens central metabolic routes by quantitatively drawing off TCA cycle intermediaries. Consequently, metabolism in C. salexigens has adapted to support this biosynthetic route. Metabolism of C. salexigens is more efficient at high salinity than at low salinity, as reflected by lower glucose consumption, lower metabolite overflow, and higher biomass yield. At low salinity, by-products (mainly gluconate, pyruvate, and acetate) accumulate extracellularly. Using [1-13C]-, [2-13C]-, [6-13C]-, and [U-13C6]glucose as carbon sources, we were able to determine the main central metabolic pathways involved in ectoines biosynthesis from glucose. C. salexigens uses the Entner-Doudoroff pathway rather than the standard glycolytic pathway for glucose catabolism, and anaplerotic activity is high to replenish the TCA cycle with the intermediaries withdrawn for ectoines biosynthesis. Metabolic flux ratios at low and high salinity were similar, revealing a certain metabolic rigidity, probably due to its specialization to support high biosynthetic fluxes and partially explaining why metabolic yields are so highly affected by salinity. This work represents an important contribution to the elucidation of specific metabolic adaptations in compatible solute-accumulating halophilic bacteria. 相似文献
107.
Xavier Calvet Sergio Lario María José Ramírez‐Lázaro Antònia Montserrat Mariela Quesada Lynsey Reeves Helen Masters David Suárez‐Lamas Marta Gallach Mireia Miquel Eva Martínez‐Bauer Isabel Sanfeliu Ferran Segura 《Helicobacter》2010,15(3):201-205
Background: Studies comparing new monoclonal fecal tests for evaluating cure of Helicobacter pylori infection after treatment are scarce. The objective was to compare the diagnostic accuracy of three monoclonal stool tests: two rapid in‐office tools –RAPID Hp StAR and ImmunoCard STAT! HpSA – and an EIA test – Amplified IDEIA Hp StAR. Materials and methods: Diagnostic reliability of the three tests was evaluated in 88 patients at least 8 weeks after H. pylori treatment. Readings of immunochromatographic tests were performed by two different observers. Sensitivity, specificity, positive and negative predictive values and 95% confidence intervals were calculated. Results: All tests presented similar performance for post‐eradication testing. Sensitivity for detecting persistent infection was 100% for both Amplified IDEIA and RAPID Hp StAR and 90% for ImmunoCard STAT! HpSA. Respective specificities were 94.9%, 92.3–93.6% and 94.9%. Negative predictive values were very high (100%, 100% and 98.7% respectively). But positive predictive values were lower, ranging from 62.5 to 71.4%. Conclusion: All monoclonal fecal tests in this series presented similar performance in the post‐treatment setting. A negative test after treatment adequately predicted cure of the infection. However, nearly a third of tests were false positive, showing a poor predictive yield for persistent infection. 相似文献
108.
Effect of testosterone on oxidative stress and cell damage induced by 3-nitropropionic acid in striatum of ovariectomized rats 总被引:4,自引:0,他引:4
Túnez I Feijóo M Collado JA Medina FJ Peña J Muñoz Mdel C Jimena I Franco F Rueda I Muntané J Montilla P 《Life sciences》2007,80(13):1221-1227
This paper evaluates the effects of testosterone (0.5 mg/kg subcutaneously (s.c.) for 8 days) on oxidative stress and cell damage induced by 3-nitropropionic acid (20 mg/kg intraperitoneally (i.p.) for 4 days) in ovariectomized rats. Gonadectomy triggered oxidative damage and cell loss, evaluated by the detection of caspase-3, whereas 3-nitropropionic acid increased the levels of oxidative stress induced by ovariectomy and prompted cell damage characterized by enhanced levels of lactate dehydrogenase. These changes were blocked by testosterone administration. Our results support the following conclusions: i) ovariectomy triggers oxidative and cell damage via caspase-3 in the striatum; ii) 3-nitropropionic acid exacerbates oxidative stress induced by ovariectomy and leads to cell damage characterized by increased levels of lactate dehydrogenase; iii) testosterone administration decreases oxidative stress and cell damage. Additionally, these data support the hypothesis that testosterone might play an important role in the onset and development of neurodegenerative diseases. 相似文献
109.
BACKGROUND AND AIMS: Invasion by alien plants may be partially related to disturbance-related increases in nutrient availability and decreases of competition with native species, and to superior competitive ability of the invader. Oxalis pes-caprae is an invasive winter geophyte in the Mediterranean Islands that reproduces vegetatively via bulbs. An investigation was made into the relative responses of O. pes-caprae and the native annual grass Lolium rigidum to nutrient availability and to competition with each other in order to understand patterns of invasion in the field. Because Oxalis accumulates oxalic acid in its leaves, which could ameliorate soil phosphorous availability, field observations were made to determine whether the presence of Oxalis alters soil P availability. METHODS: A full-factorial glasshouse experiment was conducted with nutrient availability (high and low) and competition (Lolium alone, Oxalis alone, and Lolium and Oxalis together). Plant performance was assessed by determining (1) above- and below-ground biomass at the time of Oxalis maximum biomass and (2) reproductive output of Oxalis and Lolium at the end of their respective growth cycles. Measurements were also taken for leaf N and P content. Soil samples were taken in the field from paired Oxalis-invaded and non-invaded plots located in Menorca (Balearic Islands) and available P was determined. KEY RESULTS: High nutrient availability increased Oxalis and Lolium vegetative biomass and reproductive output to a similar degree. Competition with Lolium had a much stronger negative effect on Oxalis bulb production than reduced nutrients. Lolium was a superior competitor than Oxalis; the latter did not affect Lolium maximum biomass and spike production. Significantly greater soil-P availability in Oxalis-invaded field soils relative to paired non-invaded soils suggest that Oxalis influences soil P cycling. CONCLUSIONS: Oxalis is a poor competitor. This is consistent with the preferential distribution of Oxalis in disturbed areas such as ruderal habitats, and might explain its low influence on the cover of native species in invaded sites. The results also suggest that certain disturbances (e.g. autumn ploughing) may greatly enhance Oxalis invasion. 相似文献
110.
Nucleotide variation in populations originating from the recent range expansion of a species should reflect their adaptation to new habitats as well as their demographic history. A survey of nucleotide variation at 109 noncoding X-chromosome fragments in a European population of Drosophila melanogaster allowed identifying some candidates to have been recently affected by positive selection. Adaptive changes leave a spatial differential footprint that can be used to discriminate among candidates by extending their study to neighboring regions. Here, we surveyed variation at an approximately 190-kb region spanning a locus exhibiting a significantly skewed frequency spectrum. A stretch of approximately 12 kb with reduced variation was detected within a continuously sequenced region that included the focal fragment. Moreover, the regions flanking this stretch exhibited an excess of high-frequency derived variants. Application of maximum likelihood ratio and goodness-of-fit tests suggested that the pattern of variation detected at the studied region (at cytological bands 17C-17D) might have been shaped by a recent selective change, most probably at or around the phantom gene that encodes CYP306A1, a cytochrome P450 enzyme in the ecdysteroidogenic pathway. 相似文献