全文获取类型
收费全文 | 2606篇 |
免费 | 226篇 |
专业分类
2832篇 |
出版年
2024年 | 1篇 |
2023年 | 8篇 |
2022年 | 28篇 |
2021年 | 60篇 |
2020年 | 30篇 |
2019年 | 42篇 |
2018年 | 69篇 |
2017年 | 54篇 |
2016年 | 85篇 |
2015年 | 146篇 |
2014年 | 149篇 |
2013年 | 195篇 |
2012年 | 254篇 |
2011年 | 232篇 |
2010年 | 168篇 |
2009年 | 136篇 |
2008年 | 191篇 |
2007年 | 168篇 |
2006年 | 161篇 |
2005年 | 139篇 |
2004年 | 122篇 |
2003年 | 101篇 |
2002年 | 97篇 |
2001年 | 23篇 |
2000年 | 15篇 |
1999年 | 22篇 |
1998年 | 26篇 |
1997年 | 15篇 |
1996年 | 11篇 |
1995年 | 10篇 |
1994年 | 10篇 |
1993年 | 13篇 |
1992年 | 7篇 |
1991年 | 6篇 |
1990年 | 6篇 |
1989年 | 7篇 |
1988年 | 6篇 |
1987年 | 3篇 |
1985年 | 2篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 4篇 |
1978年 | 1篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1967年 | 1篇 |
1966年 | 2篇 |
1963年 | 1篇 |
排序方式: 共有2832条查询结果,搜索用时 0 毫秒
11.
12.
Thierry Brun Jean Péduzzi Manuela Marin Caniça Gérard Paul Pierre Névot Michel Barthélémy Roger Labia 《FEMS microbiology letters》1994,120(1-2):111-117
Abstract A novel procedure was used to purify a cytosolic chitinase from Candida albicans to electrophoretic homogeneity. The results represent the first demonstration of the purification of a fungal intracellular chitinase using the criterion of a single band detected following silver-staining of a polyacrylamide gel run under denaturing conditions. Purified chitinase had pH and temperature optima of 5.0 and 50°C, respectively. Inhibition of enzyme activity by allosamidin was pH-dependent occuring maximally at pH 8.0. Phospholipids had similar marked and highly specific effects on the activities of both the purified soluble enzyme and a solubilized microsomal chitinase from C. albicans . Evidence is provided for the existence of a complex chitinolytic system in this organism. 相似文献
13.
14.
Vanessa Pitozzi Stefania Pallotta Manuela Balzi Marta Bucciolini Aldo Becciolini Piero Dolara 《Free radical research》2013,47(11):1149-1154
We used X-rays from a linear accelerator and from a low energy therapeutic source to calibrate the single cell gel electrophoresis (comet assay), a widely used method to measure DNA damage. γ-Rays from 60Co, with known efficiency in inducing DNA breakage, were used as reference. Human lymphocytes and one murine tumour cell line, F10-M3 cells, were irradiated under different experimental conditions. A similar relationship between radiation dose and induced DNA damage was obtained with γ- and X-rays. A calibration curve was constructed to convert the comet assay raw data into break frequency. The median levels of DNA breaks and oxidative damage in circulating lymphocytes from healthy volunteers were calculated to be 0.76 and 0.80 breaks/109 Da, respectively, (0.50 and 0.52 breaks/106 bp). The values of oxidative DNA damage were in the same order of magnitude as those found by others with HPLC methods. 相似文献
15.
Marie-Pierre Lézé Pascal Marchand Denis Loquet Manuela Kogler Guillaume Le Baut 《Journal of enzyme inhibition and medicinal chemistry》2013,28(6):549-557
The present study was designed to follow our pharmacomodulation work in the field of non-steroidal aromatase inhibitors. All target compounds 12a–h and 28a–h were tested in vitro for human placental aromatase inhibition, using testosterone or androstenedione as the substrate for the aromatase enzyme and the IC50 and relative potency to aminoglutethimide data are included. A SAR study indicated that 3-[(4-fluorophenyl)(1H-imidazol-1-yl)methyl]-1-ethyl-2-methyl-1H-indole (28?g) was a highly potent and selective aromatase inhibitor with IC50 value of 0.025?μM. 28?g was also a weak inhibitor of androstenedione synthesis. 相似文献
16.
Antoine Huyghe Patrice Fran?ois Andrea Mombelli Manuela Tangomo Myriam Girard Denise Baratti-Mayer Ignacio Bolivar Didier Pittet Jacques Schrenzel the Geneva Study Group on Noma 《PLoS neglected tropical diseases》2013,7(9)
Noma (cancrum oris) is a gangrenous disease of unknown etiology affecting the maxillo-facial region of young children in extremely limited resource countries. In an attempt to better understand the microbiological events occurring during this disease, we used phylogenetic and low-density microarrays targeting the 16S rRNA gene to characterize the gingival flora of acute noma and acute necrotizing gingivitis (ANG) lesions, and compared them to healthy control subjects of the same geographical and social background. Our observations raise doubts about Fusobacterium necrophorum, a previously suspected causative agent of noma, as this species was not associated with noma lesions. Various oral pathogens were more abundant in noma lesions, notably Atopobium spp., Prevotella intermedia, Peptostreptococcus spp., Streptococcus pyogenes and Streptococcus anginosus. On the other hand, pathogens associated with periodontal diseases such as Aggregatibacter actinomycetemcomitans, Capnocytophaga spp., Porphyromonas spp. and Fusobacteriales were more abundant in healthy controls. Importantly, the overall loss of bacterial diversity observed in noma samples as well as its homology to that of ANG microbiota supports the hypothesis that ANG might be the immediate step preceding noma. 相似文献
17.
Brian Ponnaiya Sally A. Amundson Shanaz A. Ghandhi Lubomir B. Smilenov Charles R. Geard Manuela Buonanno David J. Brenner 《Radiation and environmental biophysics》2013,52(4):523-530
While gene expression studies have proved extremely important in understanding cellular processes, it is becoming more apparent that there may be differences in individual cells that are missed by studying the population as a whole. We have developed a qRT-PCR protocol that allows us to assay multiple gene products in small samples, starting at 100 cells and going down to a single cell, and have used it to study radiation responses at the single-cell level. Since the accuracy of qRT-PCR depends greatly on the choice of “housekeeping” genes used for normalization, initial studies concentrated on determining the optimal panel of such genes. Using an endogenous control array, it was found that for IMR90 cells, common housekeeping genes tend to fall into one of two categories—those that are relatively stably expressed regardless of the number of cells in the sample, e.g., B2M, PPIA, and GAPDH, and those that are more variable (again regardless of the size of the population), e.g., YWHAZ, 18S, TBP, and HPRT1. Further, expression levels in commonly studied radiation-response genes, such as ATF3, CDKN1A, GADD45A, and MDM2, were assayed in 100, 10, and single-cell samples. It is here that the value of single-cell analyses becomes apparent. It was observed that the expression of some genes such as FGF2 and MDM2 was relatively constant over all irradiated cells, while that of others such as FAS was considerably more variable. It was clear that almost all cells respond to ionizing radiation but the individual responses were considerably varied. The analyses of single cells indicate that responses in individual cells are not uniform and suggest that responses observed in populations are not indicative of identical patterns in all cells. This in turn points to the value of single-cell analyses. 相似文献
18.
Cláudia Marques Diana Teixeira Ana Cunha Manuela Meireles Diogo Pestana Elisa Keating Conceição Calhau Rosário Monteiro Ana Faria 《Cell biology and toxicology》2013,29(4):293-302
Methotrexate (MTX) is broadly used in the treatment of chronic inflammatory diseases such as rheumatoid arthritis (RA). The prevalence of metabolic syndrome (MeS) in patients with this condition is relatively high. Given the importance of adipose tissue in the development of obesity metabolic complications, this study aimed to investigate the effect of methotrexate on preadipocyte proliferation, adipogenesis, and glucose uptake by adipocytes. 3T3-L1 preadipocytes proliferation was evaluated by sulforhodamine B staining and 3H-thymidine incorporation, after 24 or 48 h of treatment with MTX (0.1 and 10 μM). Preadipocytes were induced to differentiate with an appropriate adipogenic cocktail in the presence or absence of MTX. Adipogenesis was determined by measuring lipid accumulation after staining with oil red O. 3H-Deoxyglucose (3H-DG) uptake was determined by liquid scintillation counting. MTX treatment reduced culture protein content in a concentration-dependent manner and 3H-thymidine incorporation (P?<?0.05). MTX (0.1 μM) treatment increased lipid accumulation and basal 3H-DG uptake by adipocytes (P?<?0.05). In 0.1 μM MTX-treated adipocytes, insulin stimulation did not result in an increase of 3H-DG uptake, contrarily to what was observed in control cells. These results demonstrate that methotrexate interferes with adipocyte proliferation and promotes the hypertrophic growth of adipocytes. These molecular effects may have implications on metabolic profile of RA patients treated with MTX. 相似文献
19.
Federica Prati Manuela Bartolini Elena Simoni Angela De Simone Antonella Pinto Vincenza Andrisano Maria Laura Bolognesi 《Bioorganic & medicinal chemistry letters》2013,23(23):6254-6258
The anti-amyloid properties shared by several quinones inspired the design of a new series of hybrids derived from the multi-target drug candidate memoquin (1). The hybrids consist of a central benzoquinone core and a fragment taken from non-steroidal anti-inflammatory drugs, connected through polyamine linkers. The new hybrids retain the potent anti-aggregating activity of the parent 1, while exhibiting micromolar AChE inhibitory activities. Remarkably, 2, 4, (R)-6 and (S)-6 were Aβ aggregation inhibitors even more potent than 1. The balanced amyloid/cholinesterase inhibitory profile is an added value that makes the present series of compounds promising leads against Alzheimer’s disease. 相似文献
20.