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排序方式: 共有258条查询结果,搜索用时 15 毫秒
81.
Mantovani MS Bellini MF Angeli JP Oliveira RJ Silva AF Ribeiro LR 《Mutation research》2008,658(3):154-161
The polysaccharides beta-glucans occur as a principal component of the cellular walls. Some microorganisms, such as yeast and mushrooms, and also cereals such as oats and barley, are of economic interest because they contain large amounts of beta-glucans. These substances stimulate the immune system, modulating humoral and cellular immunity, and thereby have beneficial effect in fighting infections (bacterial, viral, fungal and parasitic). beta-Glucans also exhibit hypocholesterolemic and anticoagulant properties. Recently, they have been demonstrated to be anti-cytotoxic, antimutagenic and anti-tumorogenic, making them promising candidate as pharmacological promoters of health. 相似文献
82.
Daniela De Vita Andrea Angeli Fabiana Pandolfi Martina Bortolami Roberta Costi Roberto Di Santo 《Journal of enzyme inhibition and medicinal chemistry》2017,32(1):798-804
We discovered novel and selective sulfonamides/amides acting as inhibitors of the α-carbonic anhydrase (CA, EC 4.2.1.1) from the pathogenic bacterium Vibrio cholerae (VchCA). This Gram-negative bacterium is the causative agent of cholera and colonises the upper small intestine where sodium bicarbonate is present at a high concentration. The secondary sulfonamides and amides investigated here were potent, low nanomolar VchCA inhibitors whereas their inhibition of the human cytosolic isoforms CA I and II was in the micromolar range or higher. The molecules represent an interesting lead for antibacterial agents with a possibly new mechanism of action, although their CA inhibition mechanism is unknown for the moment. 相似文献
83.
Belma Zengin Kurt Busecan Aksoydan Ramin Ekhteiari Salmas Andrea Angeli 《Journal of enzyme inhibition and medicinal chemistry》2017,32(1):1042-1052
New coumaryl-carboxamide derivatives with the thiourea moiety as a linker between the alkyl chains and/or the heterocycle nucleus were synthesized and their inhibitory activity against the human carbonic anhydrase (hCA) isoforms hCA I, II, VII and IX were evaluated. While the hCA I, II and VII isoforms were not inhibited by the investigated compounds, the tumour-associated isoform hCA IX was inhibited in the high nanomolar range. 2-Oxo-N-((2-(pyrrolidin-1-yl)ethyl)carbamothioyl)-2H-chromene-3-carboxamide (e11) exhibited a selective inhibitory action against hCA IX with the Ki of 107.9?nM. In order to better understand the inhibitory profiles of studied molecules, multiscale molecular modeling approaches were used. Different molecular docking algorithms were used to investigate binding poses and predicted binding energies of studied compounds at the active sites of the CA I, II, VII and IX isoforms. 相似文献
84.
Vanda W. T. Ho Low Heng Boon Jianzhou Cui Zhou Juequn Bhuvaneshwari Shunmuganathan Rashi Gupta Nikki Y. J. Tan Xinlei Qian Kiren Purushotorman SCOPE Cohort Study Group Siew-Wai Fong Laurent Renia Lisa F. P. Ng Veronique Angeli Jinmiao Chen Brian K. Kennedy Catherine W. M. Ong Paul A. Macary 《Aging cell》2024,23(4):e14099
Although the two-dose mRNA vaccination regime provides protection against SARS-CoV-2, older adults have been shown to exhibit poorer vaccination responses. In addition, the role of vaccine-induced T-cell responses is not well characterised. We aim to assess the impact of age on immune responses after two doses of the BNT162b2 mRNA vaccine, focussing on antigen-specific T-cells. A prospective 3-month study was conducted on 15 young (median age 31 years, interquartile range (IQR) 25–35 years) and 14 older adults (median age 72 years, IQR 70–73 years). We assessed functional, neutralising antibody responses against SARS-CoV-2 variants using ACE-2 inhibition assays, and changes in B and T-cell subsets by high-dimensional flow cytometry. Antigen-specific T-cell responses were also quantified by intracellular cytokine staining and flow cytometry. Older adults had attenuated T-helper (Th) response to vaccination, which was associated with weaker antibody responses and decreased SARS-CoV-2 neutralisation. Antigen-specific interferon-γ (IFNγ)-secreting CD4+ T-cells to wild-type and Omicron antigens increased in young adults, which was strongly positively correlated with their neutralising antibody responses. Conversely, this relationship was negative in older adults. Hence, older adults' relative IFNγ-secreting CD4+ T cell deficiency might explain their poorer COVID-19 vaccination responses. Further exploration into the aetiology is needed and would be integral in developing novel vaccination strategies and improving infection outcomes in older adults. 相似文献
85.
Tatiana Sharonova Petr Zhmurov Stanislav Kalinin Alessio Nocentini Andrea Angeli Marta Ferraroni Mikhail Korsakov Claudiu T. Supuran Mikhail Krasavin 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):857
A series of sulfamide fragments has been synthesised and investigated for human carbonic anhydrase inhibition. One of the fragments showing greater selectivity for cancer-related isoforms hCA IX and XII was co-crystalized with hCA II showing significant potential for fragment periphery evolution via fragment growth and linking. These opportunities will be identified in the future via the screening of this fragment structure for co-operative carbonic anhydrase binding with other structurally diverse fragments.Open in a separate window 相似文献
86.
G Gatti R Masera R Cavallo M L Sartori D Delponte R Carignola A Salvadori A Angeli 《Steroids》1987,49(6):601-616
The role of Ca2+ in mediating the inhibition by glucocorticoids of human natural killer (NK) activity was investigated using Ca2+ entry blockers (verapamil and its desmethoxy-derivatives LU46973 and LU47093) and calmodulin antagonists (pimozide and two naphthalenesulfopamide derivatives, W-7 and W-13). Peripheral blood mononuclear (PBM) cell preparations were incubated for 20 h with 1 x 10(-6) M cortisol and these agents in various combinations (concentration range: 1 x 10(-7) - 1 x 10(-5) M) and then assayed in a direct 4-h cytolytic assay using 51Cr-labeled K 562 target cells. Exposure to cortisol led to a significant reduction of NK cell activity (about 50% with respect to the spontaneous activity). Ca2+ entry blockers displayed per se a dose-dependent depressive effect on cytotoxicity and gave significant enhancement of cortisol-dependent inhibition. Calmodulin antagonists were per se minimally effective but clearly amplified the cortisol-mediated inhibition. Raising extracellular Ca2+ by CaCl2 or intracellular Ca2+ by the ionophore A23187 yelded an appreciable reduction of these effects. Our data are compatible with the view that extracellular and intracellular Ca2+ play a role in the control of human NK cell activity. Moreover, it is conceivable that the mechanisms involved in glucocorticoid inhibition of NK cell activity involve Ca2+-dependent pathways. 相似文献
87.
We have shown previously that aldosterone injected s.c. to adrenalectomized rats has a mineralocorticoid specific action on the transmembrane movements of sodium and potassium from the rat tail artery. These effects appeared to be partly due to an unknown humoral factor. Indeed, the late in vivo effects of aldosterone on 22Na and 86Rb effluxes are suppressed or reduced after in vitro exposure to the hormone. In rats perfused with a specific antagonist of the pressor effect of vasopressin, the in vitro administration of aldosterone induced a kinetic action similar to that observed after in vitro exposure to the mineralocorticoid. Vasopressin exerts a direct action on 22Na and 86Rb effluxes. These effects were correlated in the time with the late in vivo effects of aldosterone. Moreover, vasopressin appears to potentiate the in vitro effects of aldosterone on 22Na and 86Rb effluxes. It is not yet possible to ascertain if this effect is additive or permissive. 相似文献
88.
Does the temperature sensitivity of decomposition of soil organic matter depend upon water content,soil horizon,or incubation time? 总被引:13,自引:0,他引:13
Markus Reichstein Jens-Arne Subke rew C. Angeli John D. Tenhunen 《Global Change Biology》2005,11(10):1754-1767
Several studies have shown multiple confounding factors influencing soil respiration in the field, which often hampers a correct separation and interpretation of the different environmental effects on respiration. Here, we present a controlled laboratory experiment on undisturbed organic and mineral soil cores separating the effects of temperature, drying–rewetting and decomposition dynamics on soil respiration. Specifically, we address the following questions:
- 1 Is the temperature sensitivity of soil respiration (Q10) dependent on soil moisture or soil organic matter age (incubation time) and does it differ for organic and mineral soil as suggested by recent field studies.
- 2 How much do organic and mineral soil layers contribute to total soil respiration?
- 3 Is there potential to improve soil flux models of soil introducing a multilayer source model for soil respiration?
89.
Discovering a new class of antifungal agents that selectively inhibits microbial carbonic anhydrases
Giannamaria Annunziato Laura Giovati Andrea Angeli Marialaura Pavone Sonia Del Prete Marco Pieroni 《Journal of enzyme inhibition and medicinal chemistry》2018,33(1):1537-1544
Infections caused by pathogens resistant to the available antimicrobial treatments represent nowadays a threat to global public health. Recently, it has been demonstrated that carbonic anhydrases (CAs) are essential for the growth of many pathogens and their inhibition leads to growth defects. Principal drawbacks in using CA inhibitors (CAIs) as antimicrobial agents are the side effects due to the lack of selectivity toward human CA isoforms. Herein we report a new class of CAIs, which preferentially interacts with microbial CA active sites over the human ones. The mechanism of action of these inhibitors was investigated against an important fungal pathogen, Cryptococcus neoformans, revealing that they are also able to inhibit CA in microbial cells growing in vitro. At our best knowledge, this is the first report on newly designed synthetic compounds selectively targeting β-CAs and provides a proof of concept of microbial CAs suitability as an antimicrobial drug target. 相似文献
90.