全文获取类型
收费全文 | 28109篇 |
免费 | 2058篇 |
国内免费 | 3篇 |
专业分类
30170篇 |
出版年
2023年 | 191篇 |
2022年 | 373篇 |
2021年 | 783篇 |
2020年 | 486篇 |
2019年 | 575篇 |
2018年 | 837篇 |
2017年 | 723篇 |
2016年 | 1078篇 |
2015年 | 1596篇 |
2014年 | 1753篇 |
2013年 | 2169篇 |
2012年 | 2535篇 |
2011年 | 2363篇 |
2010年 | 1485篇 |
2009年 | 1256篇 |
2008年 | 1634篇 |
2007年 | 1517篇 |
2006年 | 1449篇 |
2005年 | 1219篇 |
2004年 | 1119篇 |
2003年 | 1043篇 |
2002年 | 898篇 |
2001年 | 293篇 |
2000年 | 235篇 |
1999年 | 231篇 |
1998年 | 231篇 |
1997年 | 189篇 |
1996年 | 153篇 |
1995年 | 126篇 |
1994年 | 138篇 |
1993年 | 106篇 |
1992年 | 133篇 |
1991年 | 108篇 |
1990年 | 124篇 |
1989年 | 110篇 |
1988年 | 105篇 |
1987年 | 85篇 |
1986年 | 80篇 |
1985年 | 81篇 |
1984年 | 61篇 |
1983年 | 59篇 |
1982年 | 40篇 |
1981年 | 41篇 |
1980年 | 43篇 |
1979年 | 36篇 |
1978年 | 30篇 |
1977年 | 35篇 |
1976年 | 32篇 |
1975年 | 27篇 |
1974年 | 23篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
161.
162.
163.
Paola Palozza Rossella Simone Assunta Catalano Alma Boninsegna Volker Böhm Kati Fröhlich Maria Cristina Mele Giovanni Monego Franco O. Ranelletti 《The Journal of nutritional biochemistry》2010,21(1):34-46
The present study was undertaken to examine whether lycopene is able to counteract 7-ketocholesterol (7-KC)-induced oxidative stress and apoptosis in human macrophages. Human THP-1 macrophages were exposed to 7-KC (10–25 μM) alone and in combination with lycopene (0.5–2 μM), and we monitored changes in cell oxidative status [reactive oxygen species (ROS) production, NOX-4, hsp70 and hsp90 expressions, 8-OHdG formation] and in cell proliferation and apoptosis. After 24 h of treatment, lycopene significantly reduced the increase in ROS production and in 8-OHdG formation induced by the oxysterol in a dose-dependent manner. Moreover, the carotenoid strongly prevented the increase of NOX-4, hsp70 and hsp90 expressions as well as the phosphorylation of the redox-sensitive p38, JNK and ERK1/2 induced by the oxysterol. The attenuation of 7-KC-induced oxidative stress by lycopene coincided with a normalization of cell growth in human macrophages. Lycopene prevented the arrest in G0/G1 phase of cell cycle induced by the oxysterol and counteracted the increased expression of p53 and p21. Concomitantly, it inhibited 7-KC-induced apoptosis, by limiting caspase-3 activation and the modulatory effects of 7-KC on AKT, Bcl-2, Bcl-xL and Bax. Comparing the effects of lycopene, β-carotene and (5Z)-lycopene on ROS production, cell growth and apoptosis show that lycopene and its isomer were more effective than β-carotene in counteracting the dangerous effects of 7-KC in human macrophages. Our study suggests that lycopene may act as a potential antiatherogenic agent by preventing 7-KC-induced oxidative stress and apoptosis in human macrophages. 相似文献
164.
Santos ME das C L E Silva F Gomes KB Fernandes AP Freitas FR Faria MC Mota AP Carvalho MG 《Molecular biology reports》2011,38(5):3361-3366
Peripheral arterial disease (PAD) is an atherosclerotic disturbance characterized by a progressive obstruction of lower limb
arteries. Many risk factors associated with PAD development have being reported in the literature. The present study aimed
to investigate whether mutations in the methylenetetrahydrofolate reductase (MTHFR) or in the cystathionine beta synthase
(CBS) genes are associated with higher levels of homocysteine and the risk of PAD in patients from Brazil. This study analyzed
39 patients with PAD and 32 without PAD in whom risk factors and C677T mutations in the MTHFR gene and both 844ins68 and T833C
mutations in the CBS gene were investigated. Although higher levels of homocysteine could be observed in patients with PAD
compared to controls, no association between the increase of homocysteine and the frequency of C677T, 844ins68, and T833C
mutations could be observed. The results suggest that these mutations do not appear to be related to either homocysteine levels
or the development of the disease. However, hyperhomocysteinemia and smoking are important factors in PAD development. 相似文献
165.
Our understanding of the evolution of the insulin signaling pathway (ISP) is still incomplete. One intriguing unanswered question is the explanation of the emergence of the glucostatic role of insulin in mammals. To find out whether this is due to the development of new sets of signaling transduction elements in these organisms, or to the establishment of new interactions between pre-existing proteins, we rebuilt putative orthologous ISPs in 17 eukaryotic organisms. Then, we computed the conservation of orthologous ISPs at different levels, from sequence similarity of orthologous proteins to co-evolution of interacting domains. We found that the emergence of glucostatic role in mammals can neither be explained by the development of new sets of signaling elements, nor by the establishment of new interactions between pre-existing proteins. The comparison of orthologous IRS molecules indicates that only in mammals have they acquired their complete functionality as efficient recruiters of effector sub-pathways. 相似文献
166.
Lanzarotti E Pellizza L Bercovich A Foti M Coria SH Vazquez SC Ruberto L Hernández EA Dias RL Mac Cormack WP Cicero DO Smal C Nicolas MF Vasconcelos AT Marti MA Turjanski AG 《Journal of bacteriology》2011,193(23):6797-6798
A psychrotolerant marine bacterial strain, designated JUB59(T), was isolated from Antarctic surface seawater and classified as a new species of the genus Bizionia. Here, we present the first draft genome sequence for this genus, which suggests interesting features such as UV resistance, hydrolytic exoenzymes, and nitrogen metabolism. 相似文献
167.
Nardelli B Zaritskaya L Semenuk M Cho YH LaFleur DW Shah D Ullrich S Girolomoni G Albanesi C Moore PA 《Journal of immunology (Baltimore, Md. : 1950)》2002,169(9):4822-4830
IFN-kappa is a recently identified type I IFN that exhibits both structural and functional homology with the other type I IFN subclasses. In this study, we have investigated the effect of IFN-kappa on cells of the innate immune system by comparing cytokine release following treatment of human cells with either IFN-kappa or two recombinant IFN subtypes, IFN-beta and IFN-alpha2a. Although IFN-alpha2a failed to stimulate monocyte cytokine secretion, IFN-kappa, like IFN-beta, induced the release of several cytokines from both monocytes and dendritic cells, without the requirement of a costimulatory signal. IFN-kappa was particularly effective in inhibiting inducible IL-12 release from monocytes. Unlike IFN-beta, IFN-kappa did not induce release of IFN-gamma by PBL. Expression of the IFN-kappa mRNA was observed in resting dendritic cells and monocytes, and it was up-regulated by IFN-gamma stimulation in monocytes, while IFN-beta mRNA was minimally detectable under the same conditions. Monocyte and dendritic cell expression of IFN-kappa was also confirmed in vivo in chronic lesions of psoriasis vulgaris and atopic dermatitis. Finally, biosensor-based binding kinetic analysis revealed that IFN-kappa, like IFN-beta, binds strongly to heparin (K(d): 2.1 nM), suggesting that the cytokine can be retained close to the local site of production. The pattern of cytokines induced by IFN-kappa in monocytes, coupled with the unique induction of IFN-kappa mRNA by IFN-gamma, indicates a potential role for IFN-kappa in the regulation of immune cell functions. 相似文献
168.
Reyes Gámez-Belmonte Cristina Hernández-Chirlaque Fermín Sánchez de Medina Olga Martínez-Augustin 《生物化学与生物物理学报:疾病的分子基础》2018,1864(11):3769-3779
Tissue nonspecific alkaline phosphatase (TNAP) has a well established role in bone homeostasis and in hepatic/biliary conditions. In addition, TNAP is expressed in the inflamed intestine and is relevant to T and B lymphocyte function. TNAP KO mice are only viable for a few days, but TNAP+/? haplodeficient mice are viable. Acute pancreatitis was induced by repeated caerulein injection in WT and TNAP+/? mice. TNAP+/? mice presented an increased expression of Cxcl2, Ccl2, Selplg (P-selectin ligand), Il6 and Il1b in the pancreas. Freshly isolated acinar cells showed a dramatic upregulation of Cxcl1, Cxcl2, Ccl2, Il6, Selpg or Bax in both pancreatitis groups. TNAP+/? cells displayed a 2-fold higher expression of Cxcl2, and a smaller increase in Il6. These findings could be partly replicated by in vitro treatment of primary acinar cells with caerulein. Furthermore, the proinflammatory effect on acinar cells could be partially reproduced in wild type cells treated with the TNAP inhibitor levamisole. TNAP mRNA levels were also markedly upregulated by pancreatitis in acinar cells. Neutrophil infiltration (MRP8+ cells) and activation (IL-6 and TNF production in LPS treated primary neutrophils) were increased in TNAP+/? vs WT mice. Neutrophil depletion greatly attenuated inflammation, indicating that this cell type is mainly responsible for the higher inflammatory status of TNAP+/? mice. In conclusion, our results show that altered TNAP expression results in heightened pancreatic inflammation, which may be explained by an augmented response of neutrophils and by a higher sensitivity of acinar cells to caerulein injury. 相似文献
169.
The generation of transgenic mosquitoes with a minimal fitness load is a prerequisite for the success of strategies for controlling mosquito-borne diseases using transgenic insects. It is important to assemble as much information as possible on this subject because realistic estimates of transgene fitness costs are essential for modeling and planning release strategies. Transgenic mosquitoes must have minimal fitness costs, because such costs would reduce the effectiveness of the genetic drive mechanisms that are used to introduce the transgenes into field mosquito populations. Several factors affect fitness of transgenic mosquitoes, including the potential negative effect of transgene products and insertional mutagenesis. Studies to assess fitness of transgenic mosquitoes in the field (as opposed to the laboratory) are still needed. 相似文献
170.
Cristina Branquinho Paula MatosAna Rute Vieira Maria Margarida Prestello Ramos 《Environmental and Experimental Botany》2011,72(1):84-92
The relative impact of lichen photobiont and mycobiont was evaluated by submitting nine lichen species with: (i) different photobiont types; (ii) different lichen growth forms; and (iii) different nutrients, pH, humidity preferences; to a range of Cu concentrations (μM) supplied in repeated cycles to simulate the natural process of uptake under field conditions. The physiological performance of the photosystem II photochemical reactions was measured using Fv/Fm and the metabolic activity of the mycobiont was evaluated using ergosterol and intracellular K-loss as indicators. Lichens with higher cation exchange capacity showed higher intracellular Cu uptake and their ecology seemed to be associated with low-nutrient environments. Thus the wall and external matrix, mainly characteristic of the mycobiont partner, cannot be ignored as the first site of interaction of metals with lichens. No common intracellular Cu concentration threshold was found for the physiological impacts observed in the different species. Most physiological effects of Cu uptake in sensitive lichens occurred for intracellular Cu below 200 μg/g dw whereas more tolerant species were able to cope with intracellular Cu at least 3 times higher. Cyanobacterial lichens showed to be more sensitive to Cu uptake than green-algal lichens. Within the Trebouxia lichens, different species showed different sensitivities to Cu uptake, suggesting that the mycobiont may change the microenvironment close to the photobiont partner providing different degrees of protection. Despite the fact that the photobiont is the productive partner, the metabolic activity of the mycobiont of lichen species adapted to environments rich in nutrients, showed to be more sensitive to Cu uptake than the photochemical performance of the photobiont. 相似文献