全文获取类型
收费全文 | 7395篇 |
免费 | 479篇 |
国内免费 | 1篇 |
专业分类
7875篇 |
出版年
2024年 | 2篇 |
2023年 | 34篇 |
2022年 | 84篇 |
2021年 | 150篇 |
2020年 | 94篇 |
2019年 | 126篇 |
2018年 | 192篇 |
2017年 | 160篇 |
2016年 | 234篇 |
2015年 | 374篇 |
2014年 | 440篇 |
2013年 | 566篇 |
2012年 | 641篇 |
2011年 | 644篇 |
2010年 | 373篇 |
2009年 | 390篇 |
2008年 | 492篇 |
2007年 | 447篇 |
2006年 | 457篇 |
2005年 | 361篇 |
2004年 | 392篇 |
2003年 | 323篇 |
2002年 | 326篇 |
2001年 | 52篇 |
2000年 | 45篇 |
1999年 | 51篇 |
1998年 | 59篇 |
1997年 | 45篇 |
1996年 | 40篇 |
1995年 | 32篇 |
1994年 | 23篇 |
1993年 | 24篇 |
1992年 | 27篇 |
1991年 | 23篇 |
1990年 | 24篇 |
1989年 | 15篇 |
1988年 | 18篇 |
1987年 | 8篇 |
1986年 | 7篇 |
1985年 | 17篇 |
1984年 | 13篇 |
1983年 | 7篇 |
1982年 | 12篇 |
1981年 | 7篇 |
1980年 | 2篇 |
1979年 | 4篇 |
1978年 | 2篇 |
1977年 | 4篇 |
1974年 | 3篇 |
1967年 | 2篇 |
排序方式: 共有7875条查询结果,搜索用时 15 毫秒
121.
Silvia A. Mazzucconi 《水生昆虫》2013,35(2):129-137
Paravelia anta sp.n. from Argentina and Paraguay is described and compared with its close relative P. hungerfordi (Drake & Harris) from Brasil, which is redescribed. In addition, characteristics to separate these two from the remaining species of Paravelia are given. 相似文献
122.
Annalisa Vilasi Silvia Vilasi Rocco Romano Fausto Acernese Fabrizio Barone Maria Luisa Balestrieri Rosa Maritato Gaetano Irace Ivana Sirangelo 《Journal of cellular physiology》2013,228(6):1359-1367
A range of debilitating human diseases is known to be associated with the formation of stable highly organized protein aggregates known as amyloid fibrils. The early prefibrillar aggregates behave as cytotoxic agents and their toxicity appears to result from an intrinsic ability to impair fundamental cellular processes by interacting with cellular membranes, causing oxidative stress and increase in free Ca2+ that lead to apoptotic or necrotic cell death. However, specific signaling pathways that underlie amyloid pathogenicity remain still unclear. This work aimed to clarify cell impairment induced by amyloid aggregated. To this end, we used a combined proteomic and one‐dimensional 1H‐NMR approach on NIH‐3T3 cells exposed to prefibrillar aggregates from the amyloidogenic apomyoglobin mutant W7FW14F. The results indicated that cell exposure to prefibrillar aggregates induces changes of the expression level of proteins and metabolites involved in stress response. The majority of the proteins and metabolites detected are reported to be related to oxidative stress, perturbation of calcium homeostasis, apoptotic and survival pathways, and membrane damage. In conclusion, the combined proteomic and 1H‐NMR metabonomic approach, described in this study, contributes to unveil novel proteins and metabolites that could take part to the general framework of the toxicity induced by amyloid aggregates. These findings offer new insights in therapeutic and diagnostic opportunities. J. Cell. Physiol. 228: 1359–1367, 2013. © 2012 Wiley Periodicals, Inc. 相似文献
123.
124.
Occurrence of alternariol and alternariol monomethyl ether in beverages from the Entre Rios Province market, Argentina 总被引:1,自引:0,他引:1
Leticia Broggi Cora Reynoso Silvia Resnik Fernanda Martinez Vanesa Drunday Ángela Romero Bernal 《Mycotoxin Research》2013,29(1):17-22
One hundred and eighty five samples of red, white and rosé wines and different juices purchased in Entre Rios, Argentina, were analyzed for the Alternaria mycotoxins alternariol (AOH) and alternariol methyl ether (AME). White wines were analyzed after removal of alcohol by a nitrogen stream and concentrated. AOH in red wines was cleaned up by solid-phase extraction columns in series (octadecyl and amino propyl modified silica) and AME quantified directly on the sample. The juices were filtered and concentrated, and then all sample extracts were quantified by high performance liquid chromatography with photodiode array detector that allows confirmation through UV spectra. Method validation revealed a good sensitivity with adequate LOD and LOQ for AME and less sensitivity for AOH (i.e. white wine: AME 0.8 and 1.4 ng/mL, AOH 2 and 3.3 ng/mL; red wine: AME 0.1 and 0.2 ng/mL, AOH 4.5 and 7.5 ng/mL; apple juice: AME 1.7 and 2.8 ng/mL, AOH 5 and 9 ng/mL; other juices: AME 2.0 and 3.1 ng/mL, AOH 6 and 10 ng/mL). Recoveries in all cases were greater than 80 %. Four of 53 white wine samples were contaminated with AOH with a maximum level of 18 ng/mL, 6 of 56 samples of red wine had a maximum of 13 ng/mL, and 3 of 68 samples of juices had traces of AOH. AME was less frequently detected than AOH, and the LOD and LOQ for AME are smaller than for AOH. Only three samples of white wine and one of red wine were contaminated, but in only one white wine sample (AME 225 ng/mL) did the toxin level exceed the LOQ. 相似文献
125.
Silvia Petrezselyova Olga Kinclova-Zimmermannova Hana Sychrova 《生物化学与生物物理学报:生物膜》2013,1828(2):623-631
Cation–Cl? cotransporters (CCCs) are integral membrane proteins which catalyze the coordinated symport of Cl? with Na+ and/or K+ ions in plant and mammalian cells. Here we describe the first Saccharomyces cerevisiae CCC protein, encoded by the YBR235w open reading frame. Subcellular localization studies showed that this yeast CCC is targeted to the vacuolar membrane. Deletion of the YBR235w gene in a salt-sensitive strain (lacking the plasma-membrane cation exporters) resulted in an increased sensitivity to high KCl, altered vacuolar morphology control and decreased survival upon hyperosmotic shock. In addition, deletion of the YBR235w gene in a mutant strain deficient in K+ uptake produced a significant growth advantage over the parental strain under K+-limiting conditions, and a hypersensitivity to the exogenous K+/H+ exchanger nigericin. These results strongly suggest that we have identified a novel yeast vacuolar ion transporter mediating a K+–Cl? cotransport and playing a role in vacuolar osmoregulation. Considering its identified function, we propose to refer to the yeast YBR235w gene as VHC1 (vacuolar protein homologous to CCC family 1). 相似文献
126.
Mattia Falconi Sarah Ciccone Paola D’Arrigo Fiorenza Viani Roberto Sorge Giuseppe Novelli Patrizia Patrizi Alessandro Desideri Silvia Biocca 《Biochemical and biophysical research communications》2013
The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), the major receptor for oxidized low-density lipoprotein (ox-LDL) in endothelial cells, is overexpressed in atherosclerotic lesions. LOX-1 specific inhibitors, urgently necessary to reduce the rate of atherosclerotic and inflammation processes, are not yet available. We have designed and synthesized a new modified oxidized phospholipid, named PLAzPC, which plays to small scale the ligand-receptor recognition scheme. Molecular docking simulations confirm that PLAzPC disables the hydrophobic component of the ox-LDL recognition domain and allows the interaction of the l-lysine backbone charged groups with the solvent and with the charged/polar residues located around the edges of the LOX-1 hydrophobic tunnel. Binding assays, in a cell model system expressing human LOX-1 receptors, confirm that PLAzPC markedly inhibits ox-LDL binding to LOX-1 with higher efficacy compared to previously identified inhibitors. 相似文献
127.
Vicente Castro-Castillo Cristian Suárez-Rozas Adriana Pabón Edwin G. Pérez Bruce K. Cassels Silvia Blair 《Bioorganic & medicinal chemistry letters》2013,23(1):327-329
Some synthetic 1-azabenzanthrones (7H-dibenzo[de,h]quinolin-7-ones) are weakly to moderately cytotoxic, suggesting that they might also show antiparasitic activity. We have now tested a small collection of these compounds in vitro against a chloroquine-resistant Plasmodium falciparum strain, comparing their cytotoxicity against normal human fibroblasts. Our results indicate that 5-methoxy-1-azabenzanthrone and its 2,3-dihydro analogue have low micromolar antiplasmodial activities and showed more than 10-fold selectivity against the parasite, indicating that the dihydro compound, in particular, might serve as a lead compound for further development. 相似文献
128.
Eszter Kozma P. Suresh Jayasekara Lucia Squarcialupi Silvia Paoletta Stefano Moro Stephanie Federico Giampiero Spalluto Kenneth A. Jacobson 《Bioorganic & medicinal chemistry letters》2013,23(1):26-36
Interest is increasing in developing fluorescent ligands for characterization of adenosine receptors (ARs), which hold a promise of usefulness in the drug discovery process. The size of a strategically labeled AR ligand can be greatly increased after the attachment of a fluorophore. The choice of dye moiety (e.g. Alexa Fluor 488), attachment point and linker length can alter the selectivity and potency of the parent molecule. Fluorescent derivatives of adenosine agonists and antagonists (e.g. XAC and other heterocyclic antagonist scaffolds) have been synthesized and characterized pharmacologically. Some are useful AR probes for flow cytometry, fluorescence correlation spectroscopy, fluorescence microscopy, fluorescence polarization, fluorescence resonance energy transfer, and scanning confocal microscopy. Thus, the approach of fluorescent labeled GPCR ligands, including those for ARs, is a growing dynamic research field. 相似文献
129.
Federica Vacondio Caterina Carmi Elena Galvani Michele Bassi Claudia Silva Alessio Lodola Silvia Rivara Andrea Cavazzoni Roberta R. Alfieri Pier Giorgio Petronini Marco Mor 《Bioorganic & medicinal chemistry letters》2013,23(19):5290-5294
In the present study, a small set of reversible or irreversible 4-anilinoquinazoline EGFR inhibitors was tested in A549 cells at early (1 h) and late (8 h) time points after inhibitor removal from culture medium. A combination of assays was employed to explain the observed long-lasting inhibition of EGFR autophosphorylation. We found that EGFR inhibition at 8 h can be due, besides to the covalent interaction of the inhibitor with Cys797, as for PD168393 (2) and its prodrug 4, to the intracellular accumulation of non-covalent inhibitors by means of an active cell uptake, as for 5 and 6. Compounds 5–6 showed similar potency and duration of inhibition of EGFR autophosphorylation as the covalent inhibitor 2, while being devoid of reactive groups forming covalent bonds with protein thiols. 相似文献
130.
Guobin Cai Lisheng Deng Jian Xue Silvia N.J. Moreno Boris Striepen Yongcheng Song 《Bioorganic & medicinal chemistry letters》2013,23(7):2158-2161
The apicomplexan parasite Toxoplasma gondii, the causative agent of toxoplasmosis, is an important human pathogen. 1-Deoxy-d-xylulose-5-phosphate reductoisomerase (DXR) in the non-mevalonate isoprene biosynthesis pathway is essential to the organism and therefore a target for developing anti-toxoplasmosis drugs. In order to find potent inhibitors, we expressed and purified recombinant T. gondii DXR (TgDXR). Biochemical properties of this enzyme were characterized and an enzyme activity/inhibition assay was developed. A collection of 11 compounds with a broad structural diversity were tested against TgDXR and several potent inhibitors were identified with Ki values as low as 48 nM. Analysis of the results as well as those of Escherichia coli and Plasmodium falciparum DXR enzymes revealed a different structure–activity relationship profile for the inhibition of TgDXR. 相似文献