全文获取类型
收费全文 | 448篇 |
免费 | 20篇 |
出版年
2023年 | 7篇 |
2022年 | 4篇 |
2021年 | 9篇 |
2020年 | 9篇 |
2019年 | 7篇 |
2018年 | 17篇 |
2017年 | 29篇 |
2016年 | 27篇 |
2015年 | 22篇 |
2014年 | 29篇 |
2013年 | 41篇 |
2012年 | 44篇 |
2011年 | 37篇 |
2010年 | 24篇 |
2009年 | 16篇 |
2008年 | 21篇 |
2007年 | 33篇 |
2006年 | 9篇 |
2005年 | 19篇 |
2004年 | 16篇 |
2003年 | 23篇 |
2002年 | 6篇 |
2001年 | 5篇 |
2000年 | 3篇 |
1999年 | 2篇 |
1998年 | 1篇 |
1997年 | 2篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1993年 | 1篇 |
1977年 | 1篇 |
1971年 | 2篇 |
排序方式: 共有468条查询结果,搜索用时 109 毫秒
71.
Güleycan Lutfullahoğlu-Bal Abdurrahman Keskin Ayşe Bengisu Seferoğlu Cory D. Dunn 《Biology direct》2017,12(1):16
Background
During the generation and evolution of the eukaryotic cell, a proteobacterial endosymbiont was re-fashioned into the mitochondrion, an organelle that appears to have been present in the ancestor of all present-day eukaryotes. Mitochondria harbor proteomes derived from coding information located both inside and outside the organelle, and the rate-limiting step toward the formation of eukaryotic cells may have been development of an import apparatus allowing protein entry to mitochondria. Currently, a widely conserved translocon allows proteins to pass from the cytosol into mitochondria, but how proteins encoded outside of mitochondria were first directed to these organelles at the dawn of eukaryogenesis is not clear. Because several proteins targeted by a carboxyl-terminal tail anchor (TA) appear to have the ability to insert spontaneously into the mitochondrial outer membrane (OM), it is possible that self-inserting, tail-anchored polypeptides obtained from bacteria might have formed the first gate allowing proteins to access mitochondria from the cytosol.Results
Here, we tested whether bacterial TAs are capable of targeting to mitochondria. In a survey of proteins encoded by the proteobacterium Escherichia coli, predicted TA sequences were directed to specific subcellular locations within the yeast Saccharomyces cerevisiae. Importantly, TAs obtained from DUF883 family members ElaB and YqjD were abundantly localized to and inserted at the mitochondrial OM.Conclusions
Our results support the notion that eukaryotic cells are able to utilize membrane-targeting signals present in bacterial proteins obtained by lateral gene transfer, and our findings make plausible a model in which mitochondrial protein translocation was first driven by tail-anchored proteins.Reviewers
This article was reviewed by Michael Ryan and Thomas Simmen.72.
Gibberellic acid (GA3) is a very potent hormone whose natural occurrence in plants controls their development. Cadmium is a particularly dangerous
pollutant due to its high toxicity and great solubility in water. In this study, the effect of GA3 on Allium sativum root tip cells was investigated in the presence of cadmium. A. sativum root tip cells were exposed to CdNO3 (50, 100, 200 μM), GA3 (10-3 M), both CdNO3 and GA3. Cytogenetic analyses were performed as micronucleus (MN) assay and mitotic index (MI). Lipid peroxidation analysis was also
performed in A. sativum root tip cells for determination of membrane damage. MN exhibited a dose-dependent increase in Cd treatments in A. sativum. GA3 significantly reduced the effect of Cd on the MN frequency. MN was observed in GA3 and GA3 + 50 μm Cd treatments at very low frequency. MI slightly decreased in GA3 and GA3 + Cd treatments. MI decreased more in high concentrations of Cd than combined GA3 + Cd treatments. The high concentrations of cadmium induce MN, lipid peroxidation and lead to genotoxicity in A. sativum. Current work reveals that the effect of Cd on genotoxicity can be partially restored with GA3 application. 相似文献
73.
Fatma Yuksel Ay?e Gül Gürek ?lke Gürol Erwann Jeanneau 《Inorganica chimica acta》2008,361(8):2225-2235
N,N′-Bis[allylamino]glyoxime, N,N′-bis[anilino]glyoxime, and N,N′-bis[1,2,3,4-tetrahydro-5-naphthalenamino]glyoxime have been prepared from corresponding amines and (E,E)-dichloroglyoxime. These ligands gave orange-red compound with NiCl2 in less acidic medium (pH ∼ 5) that are bis(E,E-dioximato)nickel(II) complexes {[(E,E)-Ni(HL)2]} (1a-3a) and green compounds in acidic medium (pH ∼ 2) that are tris(E,E-dioximato)nickel(II) dichloride complexes {[(E,E)-Ni(LH2)3]Cl2} (1b-3b). The crystal structures of all complexes have been determined by X-ray diffraction on a single crystal. The study of absorption spectra of these two types of complexes shows that they may be converted to each other by addition of acids (1a-3a) or bases (1b-3b) and there is no way for the amphi form. 相似文献
74.
Continuous and intermittent 50 Hz, 1.5 mT magnetic field with the exposure period of 4 h/day for 4 days was used to investigate
its possible effect on adult guinea pigs. Tissues and plasma specimens were assessed by biochemical parameters. Malondialdehyde
(MDA), glutathione (GSH), nitric oxide (NO) levels and myeloperoxidase activity (MPO) were examined in plasma, liver and brain
tissues. All parameters were determined by spectrophotometer. While intermittent magnetic field was effective on plasma lipid
peroxidation, continuous magnetic field was found to be effective on plasma MPO activity and NO levels. Augmentation of lipid
peroxidation was also observed in liver tissue both intermittent and continuous magnetic field exposures. These results indicate
that both the intermittent and continuous magnetic field exposures affect various tissues in a distinct manner because of
having different tissue antioxidant status and responses. 相似文献
75.
Ayşegül Bayır Ahmet Ak Hasan Kara Tahir Kemal Şahin 《Biological trace element research》2009,130(1):7-12
The aim of this study was to determine the relationship between serum and cerebrospinal fluid (CSF) magnesium (Mg+2) levels, Glasgow Coma Scores (GCS), and 7-day mortality in acute stroke patients. Patients with acute ischemic or hemorrhagic
stroke arriving within the first 3 h of symptoms were included in the study. The control group consisted of healthy volunteers.
GCS was determined, and blood and CSF samples were taken in order to establish serum and CSF glucose, Mg+2, sodium, potassium, calcium, and chlorine levels. Mortality was recorded at 7 days after admission. CSF Mg+2 in the ischemic infarct group was significantly lower than in the control group (p = 0.006). CSF Mg+2 in the ischemic infarct patients with a GCS ≤ 8 were significantly lower (p = 0.002) than controls and in ischemic infarct patients with a GCS ≥9. In the ischemic stroke patients, CSF Mg+2 and GCS were significantly correlated (r = 55, p = 0.031). CSF Mg+2 levels in ischemic stroke patients who died within 7 days were significantly lower than controls, ischemic stroke patients
who survived, and hemorrhagic stroke patients who died (p = 0.002, p = 0.042, and p = 0.005, respectively). Low CSF Mg+2 levels in patients with acute ischemic stoke at admission predicted a higher 1-week mortality. 相似文献
76.
Knowledge of the protonation constants of small dipeptide is important, interesting and necessary for complete understanding
of the physiochemical behavior of dipeptide. In this study, the protonation constants of some aliphatic dipeptides (Gly–Gly, Gly–Val, Gly–Leu, Gly–Thr, Gly–Phe and Gly–Met) were studied in water and ethanol–water mixtures [20% ethanol–80% water, 40% ethanol–60% water, 60% ethanol–40% water, (v/v)]
at 25 ± 0.1°C under nitrogen atmosphere and ionic strength at 0.10 mol dm−3 by potentiometry. The constants of the systems were calculated by using BEST computer program, and distribution species diagrams
were produced using the SPE computer program. The protonation constants were influenced by changes in solvent composition,
and their variations were discussed in terms of solvent and structural properties. The concentration distribution of the various
species in ethanol–water mixtures was evaluated. 相似文献
77.
Erdal Karaoz Ayça Aksoy Selda Ayhan Ayla Eker Sarıboyacı Figen Kaymaz Murat Kasap 《Histochemistry and cell biology》2009,132(5):533-546
Bone marrow-derived mesenchymal stem cells (BM-MSCs) can differentiate into many lineages. Although the growing interest in
BM-MSCs has led to a number of characterization studies, some important biochemical and immunohistochemical properties are
still lacking. In this study, morphological and immunophenotypic properties of BM-MSCs were examined in detail. Differentiation
potential and growth kinetics of adult rat BM-MSCs were also determined. Immunohistochemistry and RT-PCR results indicated
that BM-MSCs expressed myogenic (desmin, myogenin, myosin IIa, and α-SMA), neurogenic (γ-enolase, MAP2a,b, c-fos, nestin,
GFAP and beta III tubulin), and osteogenic (osteonectin, osteocalcin, osteopontin, Runx-2, BMP-2, BMP-4 and type I collagen)
markers without stimulation towards differentiation. These expression patterns indicated why these cells can easily differentiate
into multiple lineages both in vitro and in vivo. Ultrastructural characteristics of rBM-MSCs showed more developed and metabolically
active cells. 相似文献
78.
Background
Computing the long term behavior of regulatory and signaling networks is critical in understanding how biological functions take place in organisms. Steady states of these networks determine the activity levels of individual entities in the long run. Identifying all the steady states of these networks is difficult due to the state space explosion problem.Methodology
In this paper, we propose a method for identifying all the steady states of Boolean regulatory and signaling networks accurately and efficiently. We build a mathematical model that allows pruning a large portion of the state space quickly without causing any false dismissals. For the remaining state space, which is typically very small compared to the whole state space, we develop a randomized traversal method that extracts the steady states. We estimate the number of steady states, and the expected behavior of individual genes and gene pairs in steady states in an online fashion. Also, we formulate a stopping criterion that terminates the traversal as soon as user supplied percentage of the results are returned with high confidence.Conclusions
This method identifies the observed steady states of boolean biological networks computationally. Our algorithm successfully reported the G1 phases of both budding and fission yeast cell cycles. Besides, the experiments suggest that this method is useful in identifying co-expressed genes as well. By analyzing the steady state profile of Hedgehog network, we were able to find the highly co-expressed gene pair GL1-SMO together with other such pairs.Availability
Source code of this work is available at http://bioinformatics.cise.ufl.edu/palSteady.html twocolumnfalse] 相似文献79.
We investigated the nature and signaling pathways of endothelium- and sensory-nerve ending-derived substances involved in acetylcholine-induced vasodilation in rat isolated perfused kidney. Endothelial denudation by Triton X-100 (0.2%, 0.1 ml) or depletion of afferent nerve endings by capsaicin (10(-6) mol/l) attenuated acetylcholine-induced vasodilation. When these two agents were administered together, the response to acetylcholine was completely inhibited. CGRP1 receptor blocker CGRP 8-37 (10(-7) mol/l) and adenosine A(2) receptor antagonist ZM 241 385 (10(-7) mol/l) inhibited acetylcholine-induced dilation. When indomethacin (10(-5) mol/l), a cyclooxygenase inhibitor, l-NOARG (10(-4) mol/l), a nitric oxide (NO) synthase inhibitor, and potassium chloride (30 mmol/l), to test EDHF response, were perfused simultaneously, the inhibition was greater than that was observed with each agent alone. Guanylate cyclase inhibitor ODQ (10(-5) mol/l) or protein kinase A inhibitor KT 5720 (5x10(-7) mol/l) inhibited acetylcholine-induced dilation. Gap junction uncoupler 18alpha-glycyrrhetinic acid (10(-4) mol/l) caused an uncontrollable increase in basal perfusion pressure making it impossible to test against acetylcholine-induced dilation. Our data suggest that NO, prostanoids, EDHF, and CGRP released from vascular endothelium and afferent nerve endings participate in acetylcholine-induced vasodilation and their signal transduction molecules include protein kinase A and guanylate cyclase. 相似文献
80.
Ozaltin F Ibsirlioglu T Taskiran EZ Baydar DE Kaymaz F Buyukcelik M Kilic BD Balat A Iatropoulos P Asan E Akarsu NA Schaefer F Yilmaz E Bakkaloglu A;PodoNet Consortium 《American journal of human genetics》2011,(1):139-147
Idiopathic nephrotic syndrome (INS) is a genetically heterogeneous group of disorders characterized by proteinuria, hypoalbuminemia, and edema. Because it typically results in end-stage kidney disease, the steroid-resistant subtype (SRNS) of INS is especially important when it occurs in children. The present study included 29 affected and 22 normal individuals from 17 SRNS families; genome-wide analysis was performed with Affymetrix 250K SNP arrays followed by homozygosity mapping. A large homozygous stretch on chromosomal region 12p12 was identified in one consanguineous family with two affected siblings. Direct sequencing of protein tyrosine phosphatase receptor type O (PTPRO; also known as glomerular epithelial protein-1 [GLEPP1]) showed homozygous c.2627+1G>T donor splice-site mutation. This mutation causes skipping of the evolutionarily conserved exon 16 (p.Glu854_Trp876del) at the RNA level. Immunohistochemistry with GLEPP1 antibody showed a similar staining pattern in the podocytes of the diseased and control kidney tissues. We used a highly polymorphic intragenic DNA marker-D12S1303-to search for homozygosity in 120 Turkish and 13 non-Turkish individuals in the PodoNet registry. This analysis yielded 17 candidate families, and a distinct homozygous c.2745+1G>A donor splice-site mutation in PTPRO was further identified via DNA sequencing in a second Turkish family. This mutation causes skipping of exon 19, and this introduces a premature stop codon at the very beginning of exon 20 (p.Asn888Lysfs*3) and causes degradation of mRNA via nonsense-mediated decay. Immunohistochemical analysis showed complete absence of immunoreactive PTPRO. Ultrastructural alterations, such as diffuse foot process fusion and extensive microvillus transformation of podocytes, were observed via electron microscopy in both families. The present study introduces mutations in PTPRO as another cause of autosomal-recessive nephrotic syndrome. 相似文献