全文获取类型
收费全文 | 1504篇 |
免费 | 108篇 |
出版年
2023年 | 7篇 |
2022年 | 27篇 |
2021年 | 52篇 |
2020年 | 30篇 |
2019年 | 30篇 |
2018年 | 48篇 |
2017年 | 39篇 |
2016年 | 67篇 |
2015年 | 66篇 |
2014年 | 96篇 |
2013年 | 108篇 |
2012年 | 139篇 |
2011年 | 141篇 |
2010年 | 76篇 |
2009年 | 68篇 |
2008年 | 67篇 |
2007年 | 85篇 |
2006年 | 68篇 |
2005年 | 58篇 |
2004年 | 54篇 |
2003年 | 39篇 |
2002年 | 40篇 |
2001年 | 37篇 |
2000年 | 35篇 |
1999年 | 23篇 |
1998年 | 12篇 |
1997年 | 9篇 |
1996年 | 4篇 |
1995年 | 7篇 |
1994年 | 4篇 |
1993年 | 4篇 |
1992年 | 10篇 |
1991年 | 7篇 |
1990年 | 3篇 |
1989年 | 9篇 |
1988年 | 8篇 |
1987年 | 7篇 |
1986年 | 4篇 |
1985年 | 4篇 |
1982年 | 2篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 3篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1968年 | 2篇 |
1967年 | 1篇 |
1959年 | 2篇 |
1957年 | 1篇 |
排序方式: 共有1612条查询结果,搜索用时 578 毫秒
991.
992.
Gelson Manzoni de Oliveira Manfredo Hörner Aline Machado Jorge H.S.K. Monteiro 《Inorganica chimica acta》2011,366(1):203-859
Deprotonated 3-(4-nitrophenyl)-1-phenyltriazene N-oxide reacts with YCl3·6H2O and LnCl3·6H2O (Ln = Eu, Ho, Yb) to give the monoclinic chelate complexes [Y{O2N(C6H4)NNN(O)Ph}4](Et3NH)·H2O (1) (Ph = C6H5; Et = C2H5) and [LnIII{O2N(C6H4)NNN(O)Ph}4](Et3NH)·H2O·{CH3OH∗} {LnIII = Eu (2), Ho (3), Yb∗ (4), in which the metal centers present a square antiprismatic configuration. As already observed for hydrated ammonium complexes of triazene-oxides ligands with (C6H4)−NO2 groups, multiple, effective O···H and N···H interactions hold the species in supramolecular 3D assemblies. The optical and the luminescent properties of the triazene-oxide europium complex 2 are also presented and fully discussed. 相似文献
993.
Maria Jo?o Catal?o Filipa Gil José Moniz-Pereira Madalena Pimentel 《Journal of bacteriology》2011,193(18):5002-5006
The intermolecular interactions of the mycobacteriophage Ms6 secretion chaperone with endolysin were characterized. The 384-amino-acid lysin (lysin384)-binding domain was found to encompass the N-terminal region of Gp1, which is also essential for a lysis phenotype in Escherichia coli. In addition, a GXXXG-like motif involved in Gp1 homo-oligomerization was identified within the C-terminal region. 相似文献
994.
Calvo E Mizurini DM Sá-Nunes A Ribeiro JM Andersen JF Mans BJ Monteiro RQ Kotsyfakis M Francischetti IM 《The Journal of biological chemistry》2011,286(32):27998-28010
The molecular mechanism of factor Xa (FXa) inhibition by Alboserpin, the major salivary gland anticoagulant from the mosquito and yellow fever vector Aedes albopictus, has been characterized. cDNA of Alboserpin predicts a 45-kDa protein that belongs to the serpin family of protease inhibitors. Recombinant Alboserpin displays stoichiometric, competitive, reversible and tight binding to FXa (picomolar range). Binding is highly specific and is not detectable for FX, catalytic site-blocked FXa, thrombin, and 12 other enzymes. Alboserpin displays high affinity binding to heparin (K(D) ~ 20 nM), but no change in FXa inhibition was observed in the presence of the cofactor, implying that bridging mechanisms did not take place. Notably, Alboserpin was also found to interact with phosphatidylcholine and phosphatidylethanolamine but not with phosphatidylserine. Further, annexin V (in the absence of Ca(2+)) or heparin outcompetes Alboserpin for binding to phospholipid vesicles, suggesting a common binding site. Consistent with its activity, Alboserpin blocks prothrombinase activity and increases both prothrombin time and activated partial thromboplastin time in vitro or ex vivo. Furthermore, Alboserpin prevents thrombus formation provoked by ferric chloride injury of the carotid artery and increases bleeding in a dose-dependent manner. Alboserpin emerges as an atypical serpin that targets FXa and displays unique phospholipid specificity. It conceivably uses heparin and phosphatidylcholine/phosphatidylethanolamine as anchors to increase protein localization and effective concentration at sites of injury, cell activation, or inflammation. 相似文献
995.
Zhong Y Wang Y Yang H Ballar P Lee JG Ye Y Monteiro MJ Fang S 《The Journal of biological chemistry》2011,286(39):33921-33930
The mechanism by which misfolded proteins in the endoplasmic reticulum (ER) are retrotranslocated to the cytosol for proteasomal degradation is still poorly understood. Here, we show that importin β, a well established nucleocytoplasmic transport protein, interacts with components of the retrotranslocation complex and promotes ER-associated degradation (ERAD). Knockdown of importin β specifically inhibited the degradation of misfolded ERAD substrates but did not affect turnover of non-ERAD proteasome substrates. Genetic studies and in vitro reconstitution assays demonstrate that importin β is critically required for ubiquitination of mutant α1-antitrypsin, a luminal ERAD substrate. Furthermore, we show that importin β cooperates with Ran GTPase to promote ubiquitination and proteasomal degradation of mutant α1-antitrypsin. These results establish an unanticipated role for importin β in ER protein quality control. 相似文献
996.
Rodrigues TE Souza VE Monteiro RA Gerhardt EC Araújo LM Chubatsu LS Souza EM Pedrosa FO Huergo LF 《Biochimica et biophysica acta》2011,1814(9):1203-1209
The ammonium transport family Amt/Rh comprises ubiquitous integral membrane proteins that facilitate ammonium movement across biological membranes. Besides their role in transport, Amt proteins also play a role in sensing the levels of ammonium in the environment, a process that depends on complex formation with cytosolic proteins of the P(II) family. Trimeric P(II) proteins from a variety of organisms undergo a cycle of reversible posttranslational modification according to the prevailing nitrogen supply. In proteobacteria, P(II) proteins are subjected to reversible uridylylation of each monomer. In this study we used the purified proteins from Azospirillum brasilense to analyze the effect of P(II) uridylylation on the protein's ability to engage complex formation with AmtB in vitro. Our results show that partially uridylylated P(II) trimers can interact with AmtB in vitro, the implication of this finding in the regulation of nitrogen metabolism is discussed. We also report an improved expression and purification protocol for the A. brasilense AmtB protein that might be applicable to AmtB proteins from other organisms. 相似文献
997.
Paim FC Duarte MM Costa MM Da Silva AS Wolkmer P Silva CB Paim CB França RT Mazzanti CM Monteiro SG Krause A Lopes ST 《Experimental parasitology》2011,(4):365-370
The aim of this study was to measure the levels of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin 1 (IL-1) and interleukin 6 (IL-6) in the serum of rats experimentally infected with Trypanosoma evansi and to correlate these levels with hematological parameters. Initially, 48 rats (group T) were intraperitoneally inoculated with cryopreserved blood containing 1 × 106 trypomastigotes per animal. Twenty-eight animals (group C) were used as negative controls and received 0.2 mL of saline by the same route. The experimental groups were formed according to the time after infection and the degree of parasitemia as follows: four control subgroups (C3, C5, C10 and C20) with seven non-inoculated animals each and four test subgroups (T3, T5, T10 and T20) with 10 animals each inoculated with T. evansi. The blood samples were collected by cardiac puncture at days 3 (C3, T3), 5 (C5, T5), 10 (C10, T10) and 20 (C20, T20) post-infection (PI) to perform the complete blood count and the determination of IFN-γ, TNF-α, IL-1 and IL-6 levels using an ELISA quantitative sandwich. Infected rats showed normocytic normochromic anemia during the experimental period. T. evansi infection in rats caused a serum increase (P < 0.01) of IFN-γ, TNF-α, IL-1 and IL-6 levels at days 3, 5, 10 and 20 PI compared to the controls. The multiple linear regressions showed a reduction of 24% in the hematocrit as a consequence of the increased IFN-γ, TNF-α and IL-1. Therefore, we conclude that the infection caused by T. evansi causes an increase in the pro-inflammatory cytokines. These results suggest a synergism among IL-1, TNF-α and IFN-γ contributing to the development of anemia. This increase is associated with the regulation of immune responses against the parasite. 相似文献
998.
Cotrim CA de Oliveira SC Diz Filho EB Fonseca FV Baldissera L Antunes E Ximenes RM Monteiro HS Rabello MM Hernandes MZ de Oliveira Toyama D Toyama MH 《Chemico-biological interactions》2011,189(1-2):9-16
As polyphenolic compounds isolated from plants extracts, flavonoids have been applied to various pharmaceutical uses in recent decades due to their anti-inflammatory, cancer preventive, and cardiovascular protective activities. In this study, we evaluated the effects of the flavonoid quercetin on Crotalus durissus terrificus secretory phospholipase A2 (sPLA2), an important protein involved in the release of arachidonic acid from phospholipid membranes. The protein was chemically modified by treatment with quercetin, which resulted in modifications in the secondary structure as evidenced through circular dichroism. In addition, quercetin was able to inhibit the enzymatic activity and some pharmacological activities of sPLA2, including its antibacterial activity, its ability to induce platelet aggregation, and its myotoxicity by approximately 40%, but was not able to reduce the inflammatory and neurotoxic activities of sPLA2. These results suggest the existence of two pharmacological sites in the protein, one that is correlated with the enzymatic site and another that is distinct from it. We also performed molecular docking to better understand the possible interactions between quercetin and sPLA2. Our docking data showed the existence of hydrogen-bonded, polar interactions and hydrophobic interactions, suggesting that other flavonoids with similar structures could bind to sPLA2. Further research is warranted to investigate the potential use of flavonoids as sPLA2 inhibitors. 相似文献
999.
Cristiano L.P. Oliveira Priscila R. SantosAndrea M. Monteiro Antonio M. Figueiredo Neto 《Biophysical journal》2014
This work presents a controlled study of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) structural changes due to in vitro oxidation with copper ions. The changes were studied by small-angle x-ray scattering (SAXS) and dynamic light scattering (DLS) techniques in the case of LDL and by SAXS, DLS, and Z-scan (ZS) techniques in the case of HDL. SAXS data were analyzed with a to our knowledge new deconvolution method. This method provides the electron density profile of the samples directly from the intensity scattering of the monomers. Results show that LDL particles oxidized for 18 h show significant structural changes when compared to nonoxidized particles. Changes were observed in the electrical density profile, in size polydispersity, and in the degree of flexibility of the APO-B protein on the particle. HDL optical results obtained with the ZS technique showed a decrease of the amplitude of the nonlinear optical signal as a function of oxidation time. In contrast to LDL results reported in the literature, the HDL ZS signal does not lead to a complete loss of nonlinear optical signal after 18 h of copper oxidation. Also, the SAXS results did not indicate significant structural changes due to oxidation of HDL particles, and DLS results showed that a small number of oligomers formed in the sample oxidized for 18 h. All experimental results for the HDL samples indicate that this lipoprotein is more resistant to the oxidation process than are LDL particles. 相似文献
1000.