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81.
82.
Rostislav A. Petrov Svetlana Yu. Maklakova Yan A. Ivanenkov Stanislav A. Petrov Olga V. Sergeeva Emil Yu. Yamansarov Irina V. Saltykova Igor I. Kireev Irina B. Alieva Ekaterina V. Deyneka Alina A. Sofronova Anastasiia V. Aladinskaia Alexandre V. Trofimenko Renat S. Yamidanov Sergey V. Kovalev Victor E. Kotelianski Timofey S. Zatsepin Elena K. Beloglazkina Alexander G. Majouga 《Bioorganic & medicinal chemistry letters》2018,28(3):382-387
Asialoglycoprotein receptor (ASGP-R) is a promising biological target for drug delivery into hepatoma cells. Nevertheless, there are only few examples of small-molecule conjugates of ASGP-R selective ligand equipped by a therapeutic agent for the treatment of hepatocellular carcinoma (HCC). In the present work, we describe a convenient and versatile synthetic approach to novel mono- and multivalent drug-conjugates containing N-acetyl-2-deoxy-2-aminogalactopyranose and anticancer drug – paclitaxel (PTX). Several molecules have demonstrated high affinity towards ASGP-R and good stability under physiological conditions, significant in vitro anticancer activity comparable to PTX, as well as good internalization via ASGP-R-mediated endocytosis. Therefore, the conjugates with the highest potency can be regarded as a promising therapeutic option against HCC. 相似文献
83.
Lactuca capensis reverses memory deficits in Aβ1‐42‐induced an animal model of Alzheimer's disease 下载免费PDF全文
Paula Alexandra Postu Jaures A. K. Noumedem Oana Cioanca Monica Hancianu Marius Mihasan Mitica Ciorpac Dragos Lucian Gorgan Brindusa Alina Petre Lucian Hritcu 《Journal of cellular and molecular medicine》2018,22(1):111-122
We investigated the neuropharmacological effects of the methanolic extract from Lactuca capensis Thunb. leaves (100 and 200 mg/kg) for 21 days on memory impairment in an Alzheimer's disease (AD) rat model produced by direct intraventricular delivery of amyloid‐β1‐42 (Aβ1‐42). Behavioural assays such as Y‐maze and radial arm maze test were used for assessing memory performance. Aβ1‐42 decreased cognitive performance in the behavioural tests which were ameliorated by pre‐treatment with the methanolic extract. Acetylcholinesterase activity and oxidant–antioxidant balance in the rat hippocampus were abnormally altered by Aβ1‐42 treatment while these deficits were recovered by pre‐treatment with the methanolic extract. In addition, rats were given Aβ1‐42 exhibited in the hippocampus decreased brain‐derived neurotrophic factor (BDNF) mRNA copy number and increased IL‐1β mRNA copy number which was reversed by the methanolic extract administration. These findings suggest that the methanolic extract could be a potent neuropharmacological agent against dementia via modulating cholinergic activity, increasing of BDNF levels and promoting antioxidant action in the rat hippocampus. 相似文献
84.
Alexander S. Haworth Samantha L. Hodges Alina L. Capatina Lori L. Isom Christoph G. Baumann William J. Brackenbury 《The Journal of biological chemistry》2022,298(8)
The voltage-gated Na+ channel β1 subunit, encoded by SCN1B, regulates cell surface expression and gating of α subunits and participates in cell adhesion. β1 is cleaved by α/β and γ-secretases, releasing an extracellular domain and intracellular domain (ICD), respectively. Abnormal SCN1B expression/function is linked to pathologies including epilepsy, cardiac arrhythmia, and cancer. In this study, we sought to determine the effect of secretase cleavage on β1 function in breast cancer cells. Using a series of GFP-tagged β1 constructs, we show that β1-GFP is mainly retained intracellularly, particularly in the endoplasmic reticulum and endolysosomal pathway, and accumulates in the nucleus. Reduction in endosomal β1-GFP levels occurred following γ-secretase inhibition, implicating endosomes and/or the preceding plasma membrane as important sites for secretase processing. Using live-cell imaging, we also report β1ICD-GFP accumulation in the nucleus. Furthermore, β1-GFP and β1ICD-GFP both increased Na+ current, whereas β1STOP-GFP, which lacks the ICD, did not, thus highlighting that the β1-ICD is necessary and sufficient to increase Na+ current measured at the plasma membrane. Importantly, although the endogenous Na+ current expressed in MDA-MB-231 cells is tetrodotoxin (TTX)-resistant (carried by Nav1.5), the Na+ current increased by β1-GFP or β1ICD-GFP was TTX-sensitive. Finally, we found β1-GFP increased mRNA levels of the TTX-sensitive α subunits SCN1A/Nav1.1 and SCN9A/Nav1.7. Taken together, this work suggests that the β1-ICD is a critical regulator of α subunit function in cancer cells. Our data further highlight that γ-secretase may play a key role in regulating β1 function in breast cancer. 相似文献
85.
Alina E. Minias Anna M. Brzostek Malgorzata Korycka- Machala Bozena Dziadek Piotr Minias Malini Rajagopalan Murty Madiraju Jaroslaw Dziadek 《PloS one》2015,10(5)
RNases H are involved in the removal of RNA from RNA/DNA hybrids. Type I RNases H are thought to recognize and cleave the RNA/DNA duplex when at least four ribonucleotides are present. Here we investigated the importance of RNase H type I encoding genes for model organism Mycobacterium smegmatis. By performing gene replacement through homologous recombination, we demonstrate that each of the two presumable RNase H type I encoding genes, rnhA and MSMEG4305, can be removed from M. smegmatis genome without affecting the growth rate of the mutant. Further, we demonstrate that deletion of both RNases H type I encoding genes in M. smegmatis leads to synthetic lethality. Finally, we question the possibility of existence of RNase HI related alternative mode of initiation of DNA replication in M. smegmatis, the process initially discovered in Escherichia coli. We suspect that synthetic lethality of double mutant lacking RNases H type I is caused by formation of R-loops leading to collapse of replication forks. We report Mycobacterium smegmatis as the first bacterial species, where function of RNase H type I has been found essential. 相似文献
86.
Ma?gorzata Sowiak Karolina Bródka Alina Buczyńska Marcin Cyprowski Anna Kozajda Wojciech Sobala Irena Szadkowska-Stańczyk 《Aerobiologia》2012,28(2):121-133
The project was aimed at evaluating the potential occupational exposure of swine farm workers to dust and microorganisms present
in piggery bioaerosols (especially in its respirable fraction) under various breeding conditions. Sampling was carried out
in 14 buildings located at 13 pig breeding and production farms in Poland. Concentrations of inhalable and respirable dusts
in the air of the piggeries were low (means, respectively, 1.76 and 0.23 mg/m3). The concentration of microorganisms was generally high (mean = 3.53 × 105 cfu/m3). More than 96% of determined microorganisms were bacteria (mean = 3.42 × 105 cfu/m3). The fungal concentration was distinctly lower (mean = 2.71 × 103 cfu/m3). The concentration of bacteria in the respirable fraction of bioaerosol (mean = 1.51 × 105 cfu/m3) made up for 48.2% of their total concentration, while the level of fungi in that fraction (mean = 1.50 × 103 cfu/m3) formed 68.8% of the total fungal concentration. The concentration of inhalable dust was significantly modified by the type
of breeding system. The factors that significantly affected the total concentrations of microbes and bacteria, as well as
their levels in the bioaerosols’ respirable fraction were as follows: herd size, breeding system, feeding method and the type
of ventilation system. In the case of fungi, these were the livestock breeding system and the feeding method. Moreover, there
was a high positive correlation of inhalable dust concentrations with the fungal concentration, CO2 and relative humidity. A negative correlation was found between concentrations of each microbe group and the airflow velocity.
Swine farm workers are exposed to relatively low dust concentrations and high concentrations of microorganisms, bacteria in
particular. Fungi, to a much larger extent than bacteria, are correlated with the respirable particles of a piggery bioaerosol,
which may harm the respiratory system of exposed workers. 相似文献
87.
V(D)J recombination frequencies can be profoundly affected by changes in the spacer sequence 总被引:2,自引:0,他引:2
Montalbano A Ogwaro KM Tang A Matthews AG Larijani M Oettinger MA Feeney AJ 《Journal of immunology (Baltimore, Md. : 1950)》2003,171(10):5296-5304
Each V, D, and J gene segment is flanked by a recombination signal sequence (RSS), composed of a conserved heptamer and nonamer separated by a 12- or 23-bp spacer. Variations from consensus in the heptamer or nonamer at specific positions can dramatically affect recombination frequency, but until recently, it had been generally held that only the length of the spacer, but not its sequence, affects the efficacy of V(D)J recombination. In this study, we show several examples in which the spacer sequence can significantly affect recombination frequencies. We show that the difference in spacer sequence alone of two V(H)S107 genes affects recombination frequency in recombination substrates to a similar extent as the bias observed in vivo. We show that individual positions in the spacer can affect recombination frequency, and those positions can often be predicted by their frequency in a database of RSS. Importantly, we further show that a spacer sequence that has an infrequently observed nucleotide at each position is essentially unable to support recombination in an extrachromosmal substrate assay, despite being flanked by a consensus heptamer and nonamer. This infrequent spacer sequence RSS shows only a 2-fold reduction of binding of RAG proteins, but the in vitro cleavage of this RSS is approximately 9-fold reduced compared with a good RSS. These data demonstrate that the spacer sequence should be considered to play an important role in the recombination efficacy of an RSS, and that the effect of the spacer occurs primarily subsequent to RAG binding. 相似文献
88.
Waszkiewicz N Szajda SD Zalewska A Szulc A Kępka A Minarowska A Wojewódzka-Żelezniakowicz M Konarzewska B Chojnowska S Ladny JR Zwierz K 《Folia histochemica et cytobiologica / Polish Academy of Sciences, Polish Histochemical and Cytochemical Society》2012,50(1):1-11
The relationship between alcohol consumption and glycoconjugate metabolism is complex and multidimensional. This review summarizes the advances in basic and clinical research on the molecular and cellular events involved in the metabolic effects of alcohol on glycoconjugates (glycoproteins, glycolipids, and proteoglycans). We summarize the action of ethanol, acetaldehyde, reactive oxygen species (ROS), nonoxidative metabolite of alcohol--fatty acid ethyl esters (FAEEs), and the ethanol-water competition mechanism, on glycoconjugate biosynthesis, modification, transport and secretion, as well as on elimination and catabolism processes. As the majority of changes in the cellular metabolism of glycoconjugates are generally ascribed to alterations in synthesis, transport, glycosylation and secretion, the degradation and elimination processes, of which the former occurs also in extracellular matrix, seem to be underappreciated. The pathomechanisms are additionally complicated by the fact that the effect of alcohol intoxication on the glycoconjugate metabolism depends not only on the duration of ethanol exposure, but also demonstrates dose- and regional-sensitivity. Further research is needed to bridge the gap in transdisciplinary research and enhance our understanding of alcohol- and glycoconjugate-related diseases. 相似文献
89.
90.
Salenko VB Kotnova AP Karpova NN Lyubomirskaya NV Ilyin YV 《Molecular genetics and genomics : MGG》2008,279(5):463-472
Mobile genetic elements constitute a substantial part of eukaryotic genome and play an important role in its organization
and functioning. Co-evolution of retrotransposons and their hosts resulted in the establishment of control systems employing
mechanisms of RNA interference that seem to be impossible to evade. However, “active” copies of endogenous retrovirus gypsy escape cellular control in some cases, while its evolutionary elder “inactive” variants do not. To clarify the evolutionary
relationship between “active” and “inactive” gypsy we combined two approaches: the analysis of gypsy sequences, isolated from G32 Drosophila melanogaster strain and from different Drosophila species of the melanogaster subgroup, as well as the study of databases, available on the Internet. No signs of “intermediate” (between “active” and
“inactive”) gypsy form were found in GenBank, and four full-size G32 gypsy copies demonstrated a convergence that presumably involves gene conversion. No “active” gypsy were revealed among PCR generated gypsy ORF3 sequences from the various Drosophila species indicating that “active” gypsy appeared in some population of D. melanogaster and then started to spread out. Analysis of sequences flanking gypsy variants in G32 revealed their predominantly heterochromatic location. Discrepancy between the structure of actual gypsy sites in G32 and corresponding sequences in database might indicate significant inter-strain heterochromatin diversity.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献