全文获取类型
收费全文 | 208篇 |
免费 | 12篇 |
出版年
2023年 | 1篇 |
2022年 | 6篇 |
2021年 | 10篇 |
2020年 | 12篇 |
2019年 | 14篇 |
2018年 | 14篇 |
2017年 | 9篇 |
2016年 | 14篇 |
2015年 | 8篇 |
2014年 | 12篇 |
2013年 | 17篇 |
2012年 | 19篇 |
2011年 | 19篇 |
2010年 | 8篇 |
2009年 | 1篇 |
2008年 | 6篇 |
2007年 | 5篇 |
2006年 | 2篇 |
2005年 | 5篇 |
2004年 | 4篇 |
2003年 | 2篇 |
2002年 | 4篇 |
2000年 | 2篇 |
1998年 | 2篇 |
1996年 | 1篇 |
1994年 | 1篇 |
1991年 | 6篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1984年 | 1篇 |
1982年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1973年 | 1篇 |
排序方式: 共有220条查询结果,搜索用时 46 毫秒
31.
Fereshteh Shiri Maryam Salahinejad Rahmatollah Dijoor Massoud Nejati-Yazdinejad 《Journal of receptor and signal transduction research》2018,38(2):151-165
Pathogenic Gram-negative bacteria are responsible for nearly half of the serious human infections. Hologram quantitative structure–activity relationships (HQSAR), comparative molecular field analysis (CoMFA), and comparative molecular similarity index analysis (CoMSIA) were implemented on a group of 32 of potent Gram-negative LpxC inhibitors. The most effective HQSAR model was obtained using atoms, bonds, donor, and acceptor as fragment distinction. The cross-validated correlation coefficient (q2), non-cross-validated correlation coefficient (r2), and predictive correlation coefficient (r2Pred) for test set of HQSAR model were 0.937, 0.993, and 0.892, respectively. The generated models were found to be statistically significant as the CoMFA model had (r2?=?0.967, q2?=?0.804, r2Pred?=?0.827); the CoMSIA model had (r2?=?0.963, q2?=?0.752, r2Pred?=?0.857). Molecular docking was employed to validate the results of the HQSAR, CoMFA, and CoMSIA models. Based on the obtained information, six new LpxC inhibitors have been designed. 相似文献
32.
Enhanced development of mouse single blastomeres into blastocysts via the simultaneous inhibition of TGF‐β and ERK pathways in microdroplet culture 下载免费PDF全文
Farshid Yekani Mahnaz Azarnia Fereshteh Esfandiari Seyedeh‐Nafiseh Hassani Hossein Baharvand 《Journal of cellular biochemistry》2018,119(9):7621-7630
Optimization of an in vitro culture that supports blastocyst (BL) development from single blastomeres (SBs) is essential to generate additional embryos for farm animals and humans and unravel the mechanisms that underlie totipotency. In this study, we have examined BL development from SBs that were derived from 2‐cell and 4‐cell mouse embryos in different media. Moreover, BLs were assessed for inner cell mass (ICM) by staining with Oct4. We found that BL development was improved in a lower volume of medium (1 µL) compared with a higher volume (5 µL). Furthermore, the supplementation of medium with the inhibitors of ERK1/2 and TGFβ (R2i) signaling pathways in 1 µL droplets of T6 medium improved BL development. The co‐culture of SBs with intact embryos in the presence of R2i showed more BL development and ICM to trophectoderm cell number ratio in comparison with SB culture and SB group culture. We also observed reduced total cell number, ICM, and trophectoderm cell numbers in all of the SB culture conditions versus intact embryo development. These findings might facilitate the successful generation of additional embryos for biomedical applications and elucidate the mechanisms that underlie totipotency. 相似文献
33.
Fariba Khodagholi Hadi Digaleh Fereshteh Motamedi Forough Foolad Fatemeh Shaerzadeh 《Cellular and molecular neurobiology》2016,36(6):873-881
Several pathways involved in regulation of intracellular protein integrity are known as the protein quality control (PQC) system. Molecular chaperones as the main players are engaged in various aspects of PQC system. According to the importance of these proteins in cell survival, in the present study, we traced endoplasmic reticulum-specific markers and chaperone-mediated autophagy (CMA)-associated factors as two main arms of PQC system in intra-hippocampal amyloid beta (Aβ)-injected rats during 10 days running. Data analysis from Western blot indicated that exposure to Aβ activates immunoglobulin heavy-chain-binding protein (Bip) which is the upstream regulator of unfolded protein responses (UPR). Activation of UPR system eventually led to induction of pro-apoptotic factors like CHOP, calpain, and caspase-12. Moreover, our data revealed that protein disulfide isomerase activity dramatically decreased after Aβ injection, which could be attributed to the increased levels of nitric oxide. Besides, Aβ injection induced levels of 2 members of heat shock proteins (Hsp) 70 and 90. Elevated levels of Hsps family members are accompanied by increased levels of lysosome-associated membrane protein type-2A (Lamp-2A) that are involved in CMA. Despite the reduction in CHOP, calpain, caspase-12, and Lamp-2A protein levels, the levels of molecular chaperones Bip, Hsps70, and 90 increased 10 days after Aβ injection in comparison to the control group. Based on our results, 10 days after Aβ injection, despite the activation of protective chaperones, markers associated with neurotoxicity were still elevated. 相似文献
34.
Fereshteh Azedi Somaieh Kazemnejad Amir Hassan Zarnani Masoud Soleimani Amir Shojaei Shaghayegh Arasteh 《Molecular biology reports》2017,44(1):169-182
In order to characterize the potency of menstrual blood stem cells (MenSCs) for future cell therapy of neurological disorders instead of bone marrow stem cells (BMSCs) as a well-known and conventional source of adult stem cells, we examined the in vitro differentiation potential of these stem cells into neural-like cells. The differentiation potential of MenSCs to neural cells in comparison with BMSCs was assessed under two step neural differentiation including conversion to neurosphere-like cells and final differentiation. The expression levels of Nestin, Microtubule-associated protein 2, gamma-aminobutyric acid type B receptor subunit 1 and 2, and Tubulin, beta 3 class III mRNA and/or protein were up-regulated during development of MenSCs into neurosphere-like cells (NSCs) and neural-like cells. The up-regulation level of these markers in differentiated neural-like cells from MenSCs was comparable with differentiated cells from BMSCs. Moreover, both differentiated MenSCs and BMSCs expressed high levels of potassium, calcium and sodium channel genes developing functional channels with electrophysiological recording. For the first time, we demonstrated that MenSCs are a unique cell population with differentiation ability into neural-like cells comparable to BMSCs. In addition, we have introduced an approach to generate NSCs from MenSCs and BMSCs and their further differentiation into neural-like cells in vitro. Our results hold a promise to future stem cell therapy of neurological disorders using NSCs derived from menstrual blood, an accessible source in every woman. 相似文献
35.
Comparison of cell-wall-bound extracellular proteinases (CEPs) from Lactobacillus paracasei (LBP) ssp. paracasei natural isolates BGHN14, BGAR75 and BGAR76 with Lactococcus lactis (LCL) ssp. cremoris Wg2, in their action on αS1-, β- and κ-casein was done. The CEPs of LBP strains were able to degrade αS1- and β-caseins and their caseinolytic specificity depended on the type of buffer used. These CEPs, compared with LCL Wg2,
differ in four amino acid residues in small segments predicted to be involved in substrate binding. The most striking features
of this comparison are the presence of Ala instead of Ser329 and the presence of Thr instead of Asn256 and Ala299, in the subtilisin-like region of the CEP in LBP natural isolates. Additional conservative amino acid substitution Leu to
Ile364 was found. 相似文献
36.
Kozoderović G Velhner M Jelesić Z Stojanov I Petrović T Stojanović D Golić N 《Folia microbiologica》2011,56(1):66-71
Molecular typing and resistotyping coupled with gyrA single nucleotide polymorphism (SNP) of 60 Salmonella Enteritidis (SE) isolates originated from poultry, food, and humans in Serbia is described. Molecular fingerprinting was
performed by randomly amplified polymorphic DNA (RAPD) using four primers, and the diversity index (D) was 0.688. In combination with resistotyping and gyrA SNP, D increased to 0.828. A total of 23 genetic groups were obtained. When four RAPD primers were combined, epidemic isolates from
a fast-food restaurant outbreak were clustered in a distinctive genetic group. Among 60 SE strains, three had multiple resistances
to three or more antibiotics. Nine strains were resistant to nalidixic acid (NAL; a non-fluorinated quinolone). The mutations
in quinolone resistance-determining region (QRDR) found in NAL-resistant strains were attributed to Asp87 → Asn in six strains, Asp87 → Gly in one strain, and Ser83 → Phe in one strain. One NAL-resistant strain had no mutations in QRDR, suggesting another mechanism of resistance. 相似文献
37.
M. Poyraz C.N. Banti N. Kourkoumelis M.J. Manos S. Goli?-Grdadolnik A.D. Giannoulis K. Charalabopoulos 《Inorganica chimica acta》2011,375(1):114-121
Two new mixed ligand silver(I) complexes of formulae {[Ag(tpp)3(asp)](dmf)} (1) (aspH = o-acetylsalicylic acid and tpp = triphenylphosphine) and [Ag(tpp)2(o-Hbza)] (2) (o-HbzaH = o-hydroxy-benzoic acid) were synthesized and characterized by elemental analyses, spectroscopic techniques and X-ray crystallography at ambient conditions. Three phosphorus and one carboxylic oxygen atoms from a de-protonated aspirin ligand in complex 1 and two phosphorus and two carboxylic oxygen atoms from a chelating o-Hbza anion in complex 2 form a tetrahedral geometry around Ag(I) ions in both complexes.Complexes 1 and 2 and the silver(I) nitrate, tpp, aspNa and o-HbzaH were tested for their in vitro cytotoxic activity against leiomyosarcoma cells (LMS), human breast adenocarcinoma cells (MCF-7) and normal human fetal lung fibroblasts (MRC-5) cells with Thiazolyl Blue Tetrazolium Bromide (MTT) assay. For both cell lines 1 and 2 were found to be more active than cisplatin. Additionally, 1 and 2 exhibit lower activity on cell growth proliferation of MRC-5 cells. The type of LMS cell death caused by 1 and 2 were evaluated in vitro by use of flow cytometry assay. The results show that at concentrations of 1.5 and 1.9 μΜ of complex 1, 44.1% and 69.4%, respectively of LMS cells undergo programmed cell death (apoptosis). When LMS cells were treated with 1.6 and 2.3 μM of 2, LMS cells death was by 29.6% and 81.3%, respectively apoptotic. Finally, the influence of the complexes 1 and 2, upon the catalytic peroxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase (LOX) was kinetically and theoretically studied. The binding of 1 and 2 towards LOX was also investigated by Saturation Transfer Difference (STD) 1H NMR experiments. 相似文献
38.
Sherafat MA Javan M Mozafari S Mirnajafi-Zadeh J Motamedi F 《Neurochemical research》2011,36(10):1887-1895
Multiple sclerosis (MS) is a demyelinating disease that affects the central nervous system. MS is the most common neurological
disorder in young adults with a greater incidence among females. Male gonadal hormones have a protective effect on neural
system development and myelin maturation. In this study, we investigate the effect of castration on lysolecithin-induced demyelination
and remyelination processes using visual evoked potentials, in addition to measuring the expressions of Olig2, MBP, Nogo-A
and GFAP mRNAs as oligodendrocyte or astrocyte markers; and histological assessments by myelin-specific staining. We observed
more expanded demyelination with delayed repair process in castrated rats. Expression levels of the aforementioned marker
genes confirmed histological and electrophysiological observations. Our results showed a pivotal role for endogenous male
hormones in the context of demyelinating insults. It may also account for the different prognosis of MS between male and female
genders and provide new insights for therapeutic treatments. 相似文献
39.
Safaei R Holzer AK Katano K Samimi G Howell SB 《Journal of inorganic biochemistry》2004,98(10):1607-1613
Recent studies in yeast, mouse and human cells suggest that the conserved metal binding transporters of the Cu homeostasis pathway can mediate resistance to Pt drugs in cancer cells. This review summarizes the data available from these studies. The observation that cells selected for resistance to Cu or the Pt drugs display bidirectional cross-resistance, parallel defects in the transport of Cu and the Pt drugs and altered expression of Cu transporters is consistent with the concept that the Cu homeostasis proteins regulate sensitivity to the Pt drugs by influencing their uptake, efflux and intracellular distribution. This model is supported by the finding that when mammalian and yeast cells are genetically engineered to express altered levels of the Cu transporters they exhibit altered sensitivity to Pt drugs and are defective in intracellular Pt accumulation due to altered uptake and/or efflux rates. Negative associations between the expression of ATP7A and ATP7B and the outcome of Pt therapy further support the significance of the Cu homeostasis proteins as both markers of and contributors to Pt resistance. 相似文献
40.