全文获取类型
收费全文 | 1814篇 |
免费 | 230篇 |
出版年
2022年 | 10篇 |
2021年 | 18篇 |
2020年 | 20篇 |
2019年 | 20篇 |
2018年 | 23篇 |
2017年 | 20篇 |
2016年 | 32篇 |
2015年 | 55篇 |
2014年 | 75篇 |
2013年 | 65篇 |
2012年 | 95篇 |
2011年 | 95篇 |
2010年 | 66篇 |
2009年 | 64篇 |
2008年 | 85篇 |
2007年 | 105篇 |
2006年 | 91篇 |
2005年 | 69篇 |
2004年 | 71篇 |
2003年 | 70篇 |
2002年 | 69篇 |
2001年 | 68篇 |
2000年 | 59篇 |
1999年 | 48篇 |
1998年 | 30篇 |
1997年 | 26篇 |
1996年 | 25篇 |
1995年 | 11篇 |
1994年 | 12篇 |
1993年 | 15篇 |
1992年 | 29篇 |
1991年 | 36篇 |
1990年 | 32篇 |
1989年 | 39篇 |
1988年 | 32篇 |
1987年 | 34篇 |
1986年 | 21篇 |
1985年 | 36篇 |
1984年 | 26篇 |
1983年 | 28篇 |
1982年 | 15篇 |
1981年 | 14篇 |
1980年 | 16篇 |
1979年 | 13篇 |
1978年 | 15篇 |
1977年 | 18篇 |
1975年 | 19篇 |
1974年 | 12篇 |
1973年 | 8篇 |
1972年 | 9篇 |
排序方式: 共有2044条查询结果,搜索用时 15 毫秒
81.
Johanna Marin‐Carbonne Vincent Busigny Jennyfer Miot Claire Rollion‐Bard Elodie Muller Nadja Drabon Damien Jacob Sylvain Pont Martin Robyr Tomaso R. R. Bontognali Camille Franois Stephanie Reynaud Mark Van Zuilen Pascal Philippot 《Geobiology》2020,18(3):306-325
On the basis of phylogenetic studies and laboratory cultures, it has been proposed that the ability of microbes to metabolize iron has emerged prior to the Archaea/Bacteria split. However, no unambiguous geochemical data supporting this claim have been put forward in rocks older than 2.7–2.5 giga years (Gyr). In the present work, we report in situ Fe and S isotope composition of pyrite from 3.28‐ to 3.26‐Gyr‐old cherts from the upper Mendon Formation, South Africa. We identified three populations of microscopic pyrites showing a wide range of Fe isotope compositions, which cluster around two δ56Fe values of ?1.8‰ and +1‰. These three pyrite groups can also be distinguished based on the pyrite crystallinity and the S isotope mass‐independent signatures. One pyrite group displays poorly crystallized pyrite minerals with positive Δ33S values > +3‰, while the other groups display more variable and closer to 0‰ Δ33S values with recrystallized pyrite rims. It is worth to note that all the pyrite groups display positive Δ33S values in the pyrite core and similar trace element compositions. We therefore suggest that two of the pyrite groups have experienced late fluid circulations that have led to partial recrystallization and dilution of S isotope mass‐independent signature but not modification of the Fe isotope record. Considering the mineralogy and geochemistry of the pyrites and associated organic material, we conclude that this iron isotope systematic derives from microbial respiration of iron oxides during early diagenesis. Our data extend the geological record of dissimilatory iron reduction (DIR) back more than 560 million years (Myr) and confirm that micro‐organisms closely related to the last common ancestor had the ability to reduce Fe(III). 相似文献
82.
83.
The ability to add or delete specific genes in swine will likely provide considerable benefits not just to agriculture but also to medicine, where pigs have potential as models for human disease and as organ donors. Here we have transferred nuclei from a genetically modified fibroblast cell line to porcine oocytes, matured in vitro under defined culture conditions, to create piglets expressing enhanced green fluorescent protein. The nuclear transfer-derived piglets were of normal size, although some mild symptoms of “large offspring syndrome” were evident. These experiments represent a next step towards creating swine with more useful genetic modifications. 相似文献
84.
F J Cubero A Singh E Borkham-Kamphorst Y A Nevzorova M Al Masaoudi U Haas M V Boekschoten N Gassler R Weiskirchen M Muller C Liedtke C Trautwein 《Cell death and differentiation》2013,20(11):1580-1592
Death receptor-mediated hepatocyte apoptosis is implicated in a wide range of liver diseases including viral and alcoholic hepatitis, ischemia/reperfusion injury, fulminant hepatic failure, cholestatic liver injury, as well as cancer. Deletion of NF-κB essential modulator in hepatocytes (IKKγ/Nemo) causes spontaneous progression of TNF-mediated chronic hepatitis to hepatocellular carcinoma (HCC). Thus, we analyzed the role of death receptors including TNFR1 and TRAIL in the regulation of cell death and the progression of liver injury in IKKγ/Nemo-deleted livers. We crossed hepatocyte-specific IKKγ/Nemo knockout mice (NemoΔhepa) with constitutive TNFR1−/− and TRAIL−/− mice. Deletion of TNFR1, but not TRAIL, decreased apoptotic cell death, compensatory proliferation, liver fibrogenesis, infiltration of immune cells as well as pro-inflammatory cytokines, and indicators of tumor growth during the progression of chronic liver injury. These events were associated with diminished JNK activation. In contrast, deletion of TNFR1 in bone-marrow-derived cells promoted chronic liver injury. Our data demonstrate that TNF- and not TRAIL signaling determines the progression of IKKγ/Nemo-dependent chronic hepatitis. Additionally, we show that TNFR1 in hepatocytes and immune cells have different roles in chronic liver injury–a finding that has direct implications for treating chronic liver disease. 相似文献
85.
James J. Lewis Katherine L. Fielding Alison D. Grant Violet N. Chihota Flora Popane Mariette Luttig Dorothy Muller Leonie Coetzee Gavin J. Churchyard 《PloS one》2013,8(11)
Setting
The “Thibela TB” cluster randomised trial of community-wide isoniazid preventive therapy (IPT) to reduce tuberculosis incidence in the South African gold mines.Objectives
To determine the proportion of participants eligible for IPT and the reasons and risk factors for ineligibility, to inform the scale-up of IPT.Design
Cross-sectional survey of participants in intervention clusters (mine shafts) consenting to tuberculosis screening and assessment for eligibility to start IPT.Results
Among 27,126 consenting participants, 94.7% were male, the median age was 41 years, 12.2% reported previous tuberculosis, 0.6% reported ever taking IPT and 2.5% reported currently taking antiretroviral therapy. There were 24,430 (90.1%) assessed as eligible to start IPT, of whom 23,659 started IPT. The most common reasons for ineligibility were having suspected tuberculosis that was subsequently confirmed by a positive smear and/or culture (n=705), excessive alcohol consumption (n=427) and being on tuberculosis treatment at time of initial screen (n=241). Ineligibility was associated with factors including older age, female gender, prior history of tuberculosis and being in “HIV care”. However, at least 78% were eligible for IPT in all of these sub-groups.Conclusions
The vast majority of participants in this community-wide intervention were eligible for IPT. 相似文献86.
Luciana Cadore Stefani Suzana Muller Iraci L. S. Torres Bruna Razzolini Joanna R. Rozisky Felipe Fregni Regina Markus Wolnei Caumo 《PloS one》2013,8(10)
Background
Previous studies have suggested that melatonin may produce antinociception through peripheral and central mechanisms. Based on the preliminary encouraging results of studies of the effects of melatonin on pain modulation, the important question has been raised of whether there is a dose relationship in humans of melatonin on pain modulation.Objective
The objective was to evaluate the analgesic dose response of the effects of melatonin on pressure and heat pain threshold and tolerance and the sedative effects.Methods
Sixty-one healthy subjects aged 19 to 47 y were randomized into one of four groups: placebo, 0.05 mg/kg sublingual melatonin, 0.15 mg/kg sublingual melatonin or 0.25 mg/kg sublingual melatonin. We determine the pressure pain threshold (PPT) and the pressure pain tolerance (PPTo). Quantitative sensory testing (QST) was used to measure the heat pain threshold (HPT) and the heat pain tolerance (HPTo). Sedation was assessed with a visual analogue scale and bispectral analysis.Results
Serum plasma melatonin levels were directly proportional to the melatonin doses given to each subject. We observed a significant effect associated with dose group. Post hoc analysis indicated significant differences between the placebo vs. the intermediate (0.15 mg/kg) and the highest (0.25 mg/kg) melatonin doses for all pain threshold and sedation level tests. A linear regression model indicated a significant association between the serum melatonin concentrations and changes in pain threshold and pain tolerance (R2 = 0.492 for HPT, R2 = 0.538 for PPT, R2 = 0.558 for HPTo and R2 = 0.584 for PPTo).Conclusions
The present data indicate that sublingual melatonin exerts well-defined dose-dependent antinociceptive activity. There is a correlation between the plasma melatonin drug concentration and acute changes in the pain threshold. These results provide additional support for the investigation of melatonin as an analgesic agent. Brazilian Clinical Trials Registry (ReBec): (U1111-1123-5109). IRB: Research Ethics Committee at the Hospital de Clínicas de Porto Alegre. 相似文献87.
A. Pacureanu A. Larrue M. Langer C. Olivier C. Muller M.-H. Lafage-Proust F. Peyrin 《IRBM》2013,34(1):48-52
The osteocyte cell network in bone tissue is thought to orchestrate tissue adaptation and remodeling, thus holding responsibility for tissue quality. Previously, this structure has been studied mainly in 2D and its architecture and functions are not fully elucidated. The assessment of the osteocyte system is prerequisite for deeper understanding of bone remodeling and for advances in management of bone diseases. Our goal is to enable 3D isotropic imaging of bone at cellular level and to develop algorithms for quantitative image analysis of the cell network. We recently demonstrated accurate 3D imaging of this cell structure with synchrotron radiation tomography at submicrometric scale. Due to the limited spatial resolution of the imaging system and the constraints in terms of radiation dose, the images suffer from low signal to noise ratio and the detection of the cell dendrites is challenging. Here we detail a method for enhancement of the osteocyte network in human bone from 3D microtomography images. The approach combines Hessian-based 3D line enhancement and bilateral filtering. Our method enables extraction of the interconnected cells from noisy images, preserving the integrity of the cells and of their slender dendrites. Qualitative and quantitative results are presented. 相似文献
88.
89.
Mayada Achour Marc Mousli Mahmoud Alhosin Abdulkhaleg Ibrahim Jean Peluso Christian D. Muller Valérie B. Schini-Kerth Ali Hamiche Sirano Dhe-Paganon Christian Bronner 《Biochemical and biophysical research communications》2013,430(1):208-212
Ubiquitin-like containing PHD and Ring finger 1 (UHRF1) contributes to silencing of tumor suppressor genes by recruiting DNA methyltransferase 1 (DNMT1) to their hemi-methylated promoters. Conversely, demethylation of these promoters has been ascribed to the natural anti-cancer drug, epigallocatechin-3-gallate (EGCG). The aim of the present study was to investigate whether the UHRF1/DNMT1 pair is an important target of EGCG action. Here, we show that EGCG down-regulates UHRF1 and DNMT1 expression in Jurkat cells, with subsequent up-regulation of p73 and p16INK4A genes. The down-regulation of UHRF1 is dependent upon the generation of reactive oxygen species by EGCG. Up-regulation of p16INK4A is strongly correlated with decreased promoter binding by UHRF1. UHRF1 over-expression counteracted EGCG-induced G1-arrested cells, apoptosis, and up-regulation of p16INK4A and p73. Mutants of the Set and Ring Associated (SRA) domain of UHRF1 were unable to down-regulate p16INK4A and p73, either in the presence or absence of EGCG. Our results show that down-regulation of UHRF1 is upstream to many cellular events, including G1 cell arrest, up-regulation of tumor suppressor genes and apoptosis. 相似文献
90.
Mira B. MacLennan Shannon E. Clarke Kate Perez Geoffrey A. Wood William J. Muller Jing X. Kang David W.L. Ma 《The Journal of nutritional biochemistry》2013,24(1):388-395
IntroductionDespite the advocacy that diet may be a significant contributor to cancer prevention, there is a lack of direct evidence from epidemiological and experimental studies to substantiate such claims. Experimental studies suggest that n-3 polyunsaturated fatty acids (n-3 PUFA) from marine oils may reduce breast cancer risk, however, findings are equivocal. Thus, in this study, novel transgenic mouse models were employed to provide, for the first time, direct evidence for an anti-cancer role of n-3 PUFA in mammary tumorigenesis.Methodsfat-1 Mice, which are capable of endogenous n-3 PUFA synthesis, were bred with mouse mammary tumor virus (MMTV)-neu(ndl)-YD5 mice, an aggressive breast cancer model. The resultant offspring, including novel hybrid progeny, were assessed for tumor onset, size and multiplicity as well as n-3 PUFA composition in mammary gland and tumor tissue. A complementary group of MMTV-neu(ndl)-YD5 mice were fed n-3 PUFA in the diet.ResultsMice expressing MMTV-neu(ndl)-YD5 and fat-1 displayed significant (P<.05) reductions in tumor volume (~30%) and multiplicity (~33%), as well as reduced n-6 PUFA and enriched n-3 PUFA in tumor phospholipids relative to MMTV-neu(ndl)-YD5 control mice. The effect observed in hybrid progeny was similarly observed in n-3 PUFA diet fed mice.ConclusionUsing complementary genetic and conventional dietary approaches we provide, for the first time, unequivocal experimental evidence that n-3 PUFA is causally linked to tumor prevention. 相似文献