全文获取类型
收费全文 | 460篇 |
免费 | 25篇 |
出版年
2021年 | 5篇 |
2020年 | 5篇 |
2019年 | 4篇 |
2018年 | 4篇 |
2017年 | 7篇 |
2016年 | 9篇 |
2015年 | 19篇 |
2014年 | 11篇 |
2013年 | 20篇 |
2012年 | 25篇 |
2011年 | 19篇 |
2010年 | 9篇 |
2009年 | 16篇 |
2008年 | 11篇 |
2007年 | 16篇 |
2006年 | 23篇 |
2005年 | 17篇 |
2004年 | 16篇 |
2003年 | 15篇 |
2002年 | 14篇 |
2001年 | 15篇 |
2000年 | 7篇 |
1999年 | 12篇 |
1998年 | 5篇 |
1997年 | 4篇 |
1996年 | 4篇 |
1994年 | 4篇 |
1993年 | 4篇 |
1992年 | 5篇 |
1991年 | 4篇 |
1990年 | 4篇 |
1989年 | 6篇 |
1988年 | 6篇 |
1983年 | 4篇 |
1981年 | 13篇 |
1980年 | 7篇 |
1979年 | 7篇 |
1978年 | 9篇 |
1977年 | 7篇 |
1976年 | 7篇 |
1975年 | 10篇 |
1974年 | 9篇 |
1973年 | 10篇 |
1972年 | 6篇 |
1971年 | 6篇 |
1970年 | 4篇 |
1969年 | 4篇 |
1968年 | 3篇 |
1967年 | 6篇 |
1966年 | 6篇 |
排序方式: 共有485条查询结果,搜索用时 15 毫秒
41.
42.
The economics surrounding five algae-to-fuels process scenarios were examined. The different processes modeled were as follows: an open pond producing either triacylglycerides (TAG) or free fatty acid methyl ester (FAME), a solar-lit photobioreactor producing either FAME or free fatty acids (FFA), and a light emitting diode irradiated (LED-lighted) photobioreactor producing TAG. These processes were chosen to represent both classical and esoteric approaches presented in the open literature. Viable (or suggested) processing techniques to liberate and purify (and convert) the microalgal triacylglycerides were then modeled to accompany each growth option. The investment and cost per kg of fuel or fuel precursor for each process was determined. The open pond produced TAG at ~$7.50/kg, while the process using the LED-lit photobioreactor produced TAG at ~$33/kg. The scenario containing the solar-lit photobioreactor produced FAME at ~$25/kg, while the open pond produced FAME at ~$4/kg. The scenario containing the solar-lit photobioreactor produced FFA at ~$29/kg. The open pond scenarios appear to be closest to the $1/kg pricepoint at this time, and thus are the most viable economic options. Future technological advancements that reduce the cost of bioreactor vessels, LED lighting, and solvent recovery, may reduce the oil production costs of these scenarios to a more attractive level. 相似文献
43.
Improta G Zupa A Fillmore H Deng J Aieta M Musto P Liotta LA Broaddus W Petricoin EF Wulfkuhle JD 《Journal of proteome research》2011,10(7):3089-3097
Brain metastases are the most common fatal complication of systemic cancer, especially of lung (40-50%) and breast (20-30%) cancers. In this era of personalized therapy, there is a critical need to uncover the signaling architecture of brain metastases; however, little is known about what signaling pathways are activated in the context of the brain microenvironment. Using a unique study set of 42 brain metastases from patients with breast or nonsmall cell lung cancer (NSCLC), the phosphorylation/activation states of 128 key signaling proteins involved in cancer signaling were measured in laser capture microdissected tumor epithelium using reverse phase protein microarray (RPMA) technology. Distinct pathway activation subgroups from both breast and lung metastases were underpinned by, among others, ERBB2, AKT, mTOR, EGFR, SMAD, and ERK-p38 signaling. Breast cancer metastases showed significantly (p < 0.05) higher activation of the c-ERBB2/IGFR-AKT pathway network compared to NSCLC metastases, whereas NSCLC metastases to the brain exhibited higher relative levels of many members of the EGFR-ERK signaling network. Protein pathway activation mapping using RPMA revealed both the heterogeneity of signaling networks in brain metastases that would require a prior stratification to targeted therapies as well as the requirement of direct analysis of the metastatic lesion. 相似文献
44.
Canonici A Siret C Pellegrino E Pontier-Bres R Pouyet L Montero MP Colin C Czerucka D Rigot V André F 《PloS one》2011,6(3):e18427
Intestinal epithelial cell damage is frequently seen in the mucosal lesions of inflammatory bowel diseases such as ulcerative colitis or Crohn's disease. Complete remission of these diseases requires both the cessation of inflammation and the migration of enterocytes to repair the damaged epithelium. Lyophilized Saccharomyces boulardii (Sb, Biocodex) is a nonpathogenic yeast widely used as a therapeutic agent for the treatment and prevention of diarrhea and other gastrointestinal disorders. In this study, we determined whether Sb could accelerate enterocyte migration. Cell migration was determined in Sb force-fed C57BL6J mice and in an in vitro wound model. The impact on α2β1 integrin activity was assessed using adhesion assays and the analysis of α2β1 mediated signaling pathways both in vitro and in vivo. We demonstrated that Sb secretes compounds that enhance the migration of enterocytes independently of cell proliferation. This enhanced migration was associated with the ability of Sb to favor cell-extracellular matrix interaction. Indeed, the yeast activates α2β1 integrin collagen receptors. This leads to an increase in tyrosine phosphorylation of cytoplasmic molecules, including focal adhesion kinase and paxillin, involved in the integrin signaling pathway. These changes are associated with the reorganization of focal adhesion structures. In conclusion Sb secretes motogenic factors that enhance cell restitution through the dynamic regulation of α2β1 integrin activity. This could be of major importance in the development of novel therapies targeting diseases characterized by severe mucosal injury, such as inflammatory and infectious bowel diseases. 相似文献
45.
Tota B Amelio D Pellegrino D Ip YK Cerra MC 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2005,142(2):164-177
In the mammalian heart, intracardiac nitric oxide (NO) regulates in an autocrine-paracrine manner cardiac function in the beat-to-beat response (Starling's law of the heart), short-term response (phasic control, e.g. excitation-contraction coupling, responses to neurotransmitters and endocrines) and long-term response (tonic control by altering gene expression). This trio of NO temporal-dependent actions has a long evolutionary history, as we have documented in the prototypic vertebrate heart, the teleost heart. This heart shares a common structural and functional scenario with higher vertebrate hearts exhibiting, at the same time, differences in myoarchitecture (trabecular vs. compact type), blood supply (lacunary vs. vascular) and pumping performance (sensitivity to filling pressure), thus providing challenging opportunities for revealing aspects of unity and diversity of cardiac NO in vertebrates. Using in vitro working teleost heart preparations we have shown that, under basal conditions, NO through a cGMP-mediated mechanism modulates ventricular performance (negative inotropism) and remarkably increases the sensitivity to filling pressure (i.e. the Frank-Starling response). NO-cGMP mechanism also influences the short-term response elicited by inotropic agents such as acetylcholine and angiotensin II. A role of NO in long-term cardiac adaptation is illustrated by morphologic evidence (e.g. NOS immuno-localization in phylogenetically distant species) which emphasizes the importance of NO in reshaping the angio-myoarchitecture of the fish heart ventricle (i.e. compensation for regional heterogeneity). Finally, by studying the avascular hearts of teleosts and amphibians that lack vascular endothelium, a relevant role of endocardial endothelium-NO signalling in intracavitary regulation of myocardial performance has been firmly established, thus revealing its early evolutionary role in non-mammalian vertebrates. 相似文献
46.
A synthetic water-soluble meso-tetra(2,6-dichloro-3-sulfonatophenyl)porphyrinate of iron(III) chloride, Fe(TDCPPS)Cl, was employed as a biomimetic catalyst in the oxidative coupling of terrestrial humic materials. High-performance size-exclusion chromatography (HPSEC), solid-state nuclear magnetic resonance (CPMAS-(13)C NMR), electron paramagnetic resonance (EPR), and diffuse reflectance infrared spectroscopy (DRIFT) were used to follow conformational and structural changes brought about in different humic materials by the oxidative coupling. Increase in apparent weight-average molecular weight (Mw(a)) occurred invariably for all humic substances with the oxidative polymerization catalyzed by Fe(TDCPPS)Cl. HPSEC further showed that the polymerization reaction turned the loosely bound humic supramolecular structures into more stable conformations which could no longer be disrupted by the disaggregating effect of acetic acid. DRIFT spectroscopy suggested the formation of new alkyl and aromatic ethers following the oxidative coupling with the biomimetic catalyst. CPMAS-(13)C NMR and EPR spectra suggested a reduced molecular mobility of humic components and enhanced stabilization of free radicals in larger oxidized fragments. All findings concur in indicating that the biomimetic catalysis by Fe(TDCPPS)Cl increased the molecular mass and chemical rigidity of humic materials by formation of intermolecular covalent bonds via a free-radical mechanism. The development of a technology based on oxidative polymerization by biomimetic catalysis may be of importance in controlling the properties and reactivity of humic matter for industrial and environmental applications. 相似文献
47.
BACKGROUND AND AIMS: Soil water deficit is a major abiotic stress with severe consequences for the development, productivity and quality of crops. However, it is considered a positive factor in grapevine management (Vitis vinifera), as it has been shown to increase grape quality. The effects of soil water deficit on organogenesis, morphogenesis and gas exchange in the shoot were investigated. METHODS: Shoot organogenesis was analysed by distinguishing between the various steps in the development of the main axis and branches. Several experiments were carried out in pots, placed in a greenhouse or outside, in southern France. Soil water deficits of various intensities were imposed during vegetative development of the shoots of two cultivars ('Syrah' and 'Grenache N'). KEY RESULTS: All developmental processes were inhibited by soil water deficit, in an intensity-dependent manner, and sensitivity to water stress was process-dependent. Quantitative relationships with soil water were established for all processes. No difference was observed between the two cultivars for any criterion. The number of leaves on branches was particularly sensitive to soil water deficit, which rapidly and strongly reduced the rate of leaf appearance on developing branches. This response was not related to carbon availability, photosynthetic activity or the soluble sugar content of young expanding leaves. The potential number of branches was not a limiting factor for shoot development. CONCLUSIONS: The particularly high sensitivity to soil water deficit of leaf appearance on branches indicates that this process is a major determinant of the adaptation of plant leaf area to soil water deficit. The origin of this particular developmental response to soil water deficit is unclear, but it seems to be related to constitutive characteristics of branches rather than to competition for assimilates between axes differing in sink strength. 相似文献
48.
Marchionni I Paffi A Pellegrino M Liberti M Apollonio F Abeti R Fontana F D'Inzeo G Mazzanti M 《Biochimica et biophysica acta》2006,1758(5):597-605
Alteration of membrane surface charges represents one of the most interesting effects of the electromagnetic exposure on biological structures. Some evidence exists in the case of extremely low frequency whereas the same effect in the radiofrequency range has not been detected. Changes in transmembrane voltages are probably responsible for the mobilization of intracellular calcium described in some previous studies but not confirmed in others. These controversial results may be due to the cell type under examination and/or to the permeability properties of the membranes. According to such a hypothesis, calcium oscillations would be a secondary effect due to the induced change in the membrane voltage and thus dependent on the characteristics of ionic channels present in a particular preparation. Calcium increases could suggest more than one mechanism to explain the biological effects of exposure due to the fact that all the cellular pathways using calcium ions as a second messenger could be, in theory, disturbed by the electromagnetic field exposure. In the present work, we investigate the early phase of the signal transmission in the peripheral nervous system. We present evidence that the firing rate of rat sensory neurons can be modified by 50/60 Hz magnetic field but not by low level 900 MHz fields. The action of the 50/60 Hz magnetic field is biphasic. At first, the number of action potentials increases in time. Following this early phase, the firing rate decreases more rapidly than in control conditions. The explanation can be found at the single-channel level. Dynamic action current recordings in dorsal root ganglion neurons acutely exposed to the electromagnetic field show increased functionality of calcium channels. In parallel, a calcium-activated potassium channel is able to increase its mean open time. 相似文献
49.
Evidence that low doses of Taxol enhance the functional transactivatory properties of p53 on p21 waf promoter in MCF-7 breast cancer cells 总被引:2,自引:0,他引:2
Panno ML Giordano F Mastroianni F Morelli C Brunelli E Palma MG Pellegrino M Aquila S Miglietta A Mauro L Bonofiglio D Andò S 《FEBS letters》2006,580(9):2371-2380
In the present study, we evidence how in breast cancer cells low doses of Taxol for 18 h determined the upregulation of p53 and p21 waf expression concomitantly with a decrease of the anti-apoptotic Bcl-2. P53 and its gene product, the mdm2 protein, in treated cells exhibits a prevalent nuclear compartmentalization, thus potentiating p53 transactivatory properties. Indeed, the most important finding of this study consists with the evidence that Taxol at lower concentrations is able to produce the activation of p21 promoter via p53. Prolonged exposure of MCF-7 cells to Taxol (48 h) resulted in an increased co-association between p21 and PCNA compared to control and this well fits with the simultaneous block of cell cycle into the G2/M phase. 相似文献
50.
Single-channel recordings were used to study the modulation of stretch-activated channels (SACs) by intracellular adenosine nucleotides in identified leech neurons. These channels exhibited two activity modes, spike-like (SL) and multiconductance (MC), displaying different polymodal activation. In the absence of mechanical stimulation, internal perfusion of excised patches with ATP induced robust and reversible activation of the MC but not of the SL mode. The ATP effect on channel activity was dose-dependent within a range of 1 μM-1 mM and was induced at different values of intracellular pH and Ca2+. The non-hydrolyzable ATP analog AMP-PNP, ATP without Mg2+ or ADP also effectively enhanced MC activity. Adenosine mimicked the effect of its nucleotides. At negative membrane potentials, both ATP and adenosine activated the channel. Moreover, ATP but not adenosine induced a flickering block. Addition of cAMP during maximal ATP activation completely and reversibly inhibited the channel, with activation and deactivation times of minutes. However, cAMP alone only induced a weak and rapid channel activation, without inhibitory effects. The expression of these channels in the growth cones of leech neurons, their permeability to Ca2+ and their sensitivity to intracellular cAMP are consistent with a role in the Ca2+ oscillations associated with cell growth. 相似文献