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991.
Depletion of E-cadherin disrupts establishment but not maintenance of cell junctions in Madin-Darby canine kidney epithelial cells 总被引:1,自引:0,他引:1
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E-cadherin forms calcium-dependent homophilic intercellular adhesions between epithelial cells. These contacts regulate multiple aspects of cell behavior, including the organization of intercellular tight junctions (TJs). To distinguish between the roles of E-cadherin in formation versus maintenance of junctions, Madin-Darby canine kidney (MDCK) cells were depleted of E-cadherin by RNA interference. Surprisingly, reducing E-cadherin expression had little effect on the protein levels or localization of adherens junction (AJ) or TJ markers. The cells underwent morphological changes, as the normally flat apical surface swelled into a dome. However, apical-basal polarity was not compromised, transmembrane resistance was normal, and zonula occludin protein 1 dynamics at the TJs were unchanged. Additionally, an E-cadherin/Cadherin-6 double knockdown also failed to disrupt established TJs, although beta-catenin was lost from the cell cortex. Nevertheless, cells depleted of E-cadherin failed to properly reestablish cell polarity after junction disassembly. Recovery of cell-cell adhesion, transepithelial resistance, and the localization of TJ and AJ markers were all delayed. In contrast, depletion of alpha-catenin caused long-term disruption of junctions. These results indicate that E-cadherin and Cadherin-6 function as a scaffold for the construction of polarized structures, and they become largely dispensable in mature junctions, whereas alpha-catenin is essential for the maintenance of functional junctions. 相似文献
992.
Lack of adenomatous polyposis coli protein correlates with a decrease in cell migration and overall changes in microtubule stability
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Kroboth K Newton IP Kita K Dikovskaya D Zumbrunn J Waterman-Storer CM Näthke IS 《Molecular biology of the cell》2007,18(3):910-918
Most sporadic colorectal tumors carry truncation mutations in the adenomatous polyposis coli (APC) gene. The APC protein is involved in many processes that govern gut tissue. In addition to its involvement in the regulation of beta-catenin, APC is a cytoskeletal regulator with direct and indirect effects on microtubules. Cancer-related truncation mutations lack direct and indirect binding sites for microtubules in APC, suggesting that loss of this function contributes to defects in APC-mutant cells. In this study, we show that loss of APC results in disappearance of cellular protrusions and decreased cell migration. These changes are accompanied by a decrease in overall microtubule stability and also by a decrease in posttranslationally modified microtubules in the cell periphery particularly the migrating edge. Consistent with the ability of APC to affect cell shape, the overexpression of APC in cells can induce cellular protrusions. These data demonstrate that cell migration and microtubule stability are linked to APC status, thereby revealing a weakness in APC-deficient cells with potential therapeutic implications. 相似文献
993.
Induction of heat shock proteins in differentiated human and rodent neurons by celastrol 总被引:1,自引:0,他引:1
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Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis have been termed protein misfolding disorders that are characterized by the neuronal accumulation of protein aggregates. Manipulation of the cellular stress-response involving induction of heat shock proteins (Hsps) in differentiated neurons offers a therapeutic strategy to counter conformational changes in neuronal proteins that trigger pathogenic cascades resulting in neurodegenerative diseases. Hsps are protein repair agents that provide a line of defense against misfolded, aggregation-prone proteins. These proteins are not induced in differentiated neurons by conventional heat shock. We have found that celastrol, a quinine methide triterpene, induced expression of a wider set of Hsps, including Hsp70B', in differentiated human neurons grown in tissue culture compared to cultured rodent neuronal cells. Hence the beneficial effect of celastrol against human neurodegenerative diseases may exceed its potential in rodent models of these diseases. 相似文献
994.
Moll SJ Jones CJ Crocker IP Baker PN Heazell AE 《Apoptosis : an international journal on programmed cell death》2007,12(9):1611-1622
Pre-eclampsia and intrauterine growth restriction are associated with increased apoptosis of placental villous trophoblast.
This may result from placental hypoperfusion, leading to the generation of reactive oxygen species (ROS). Apoptosis can be
induced in villous trophoblast following exposure to oxidative stress. Epidermal growth factor (EGF) reduces trophoblast apoptosis
resulting from exposure to hypoxia. We hypothesised that exposure to hydrogen peroxide, a potent generator of ROS, would induce
apoptosis in term placental villous explants and that this could be reduced by treatment with EGF. Placental explants were
taken from normal term pregnancies and exposed to increasing doses of hydrogen peroxide (0–1,000 μM) or to a combination of
increasing doses of hydrogen peroxide and EGF (0–100 ng/ml) for either 6 or 48 h. Apoptosis was assessed by TUNEL, proliferation
by Ki-67 immunostaining, necrosis by lactate dehydrogenase activity and trophoblast differentiation by human chorionic gonadotrophin
(hCG) secretion in conditioned culture media. Immunoperoxidase staining was performed to identify phosphorylated-AKT (p-AKT)
and phosphorylated-PI3 kinase (p-PI3k). Exposure to 1,000 μM hydrogen peroxide for 48 h induced apoptosis in placental explants.
The increase in TUNEL positive nuclei predominantly localised to syncytiotrophoblast. The amount of apoptosis was reduced
to control levels by treatment with 10 and 100 ng/ml EGF. Proliferation of cytotrophoblasts within villous explants was significantly
reduced following exposure to 1,000 μM hydrogen peroxide, this was restored to control levels by simultaneous treatment with
10 or 100 ng/ml EGF. Neither exposure to hydrogen peroxide or EGF altered the amount of necrosis. There was increased immunostaining
for pPI3K following treatment with EGF. This study shows that apoptosis may be induced in villous trophoblast following exposure
to ROS, and demonstrates the anti-apoptotic effect of EGF in trophoblast, the maintenance of which is essential for normal
pregnancy. 相似文献
995.
Phylocomposer and phylodirector: analysis and visualization of transducer indel models 总被引:1,自引:0,他引:1
Holmes I 《Bioinformatics (Oxford, England)》2007,23(23):3263-3264
Finite-state string transducers are probabilistic tools similar to Hidden Markov Models that can be systematically extended to large number of sequences related by indel and substitution processes on phylogenetic trees. The number of states in such models grows exponentially with the number of nodes in the tree, with the consequence that even quite small trees can be difficult to analyze or visualize. Here, we present two tools, phylocomposer and phylodirector, for working with string transducers. The former tool implements previously described composition algorithms for extending transducers to arbitrary tree topologies, while the latter generates short animations for arbitrary input alignments and phylogenetic trees, illustrating the state path through the composed transducer. AVAILABILITY: Phylocomposer and phylodirector are freely available at http://biowiki.org/PhyloComposer and http://biowiki.org/PhyloDirector 相似文献
996.
MPP is a Java application, encompassing both new and established algorithms, for the analysis of gene and marker content datasets arising from high-throughput microarray techniques. MPP analyses flat file output from microarray experiments to determine the probability of the presence or absence of genes or markers within a genome. MPP can construct gene or marker content datasets for a number of genomes and can use the data to estimate an evolutionary tree or network. Results from gene content analyses may be validated by comparing them to known gene contents. MPP was initially developed to analyse data derived from comparative genome hybridization (CGH) microarray experiments in fungi and bacteria. It has recently been adapted to analyse retrotransposon-based insertion polymorphism (RBIP) marker scores derived from tagged microarray marker (TAM) experiments in pea. New analytical procedures may be added easily to MPP as plugins in order to increase the scope of the software. AVAILABILITY: MPP source code, executables and online help are available at http://cbr.jic.ac.uk/dicks/software/ 相似文献
997.
MOTIVATION: The numbers of finished and ongoing genome projects are increasing at a rapid rate, and providing the catalog of genes for these new genomes is a key challenge. Obtaining a set of well-characterized genes is a basic requirement in the initial steps of any genome annotation process. An accurate set of genes is needed in order to learn about species-specific properties, to train gene-finding programs, and to validate automatic predictions. Unfortunately, many new genome projects lack comprehensive experimental data to derive a reliable initial set of genes. RESULTS: In this study, we report a computational method, CEGMA (Core Eukaryotic Genes Mapping Approach), for building a highly reliable set of gene annotations in the absence of experimental data. We define a set of conserved protein families that occur in a wide range of eukaryotes, and present a mapping procedure that accurately identifies their exon-intron structures in a novel genomic sequence. CEGMA includes the use of profile-hidden Markov models to ensure the reliability of the gene structures. Our procedure allows one to build an initial set of reliable gene annotations in potentially any eukaryotic genome, even those in draft stages. AVAILABILITY: Software and data sets are available online at http://korflab.ucdavis.edu/Datasets. 相似文献
998.
The green tea compound, (-)-epigallocatechin-3-gallate downregulates N-cadherin and suppresses migration of bladder carcinoma cells 总被引:1,自引:0,他引:1
Rieger-Christ KM Hanley R Lodowsky C Bernier T Vemulapalli P Roth M Kim J Yee AS Le SM Marie PJ Libertino JA Summerhayes IC 《Journal of cellular biochemistry》2007,102(2):377-388
Green tea has been reported as potential dietary protection against numerous cancers and has been shown to have activity in bladder tumor inhibition in different animal models. The goal of this study was to examine the effects of (-)-epigallocatechin gallate (EGCG-the major phytochemical in green tea) on growth inhibition and behavior of human bladder carcinoma cells and to identify the altered signaling pathway(s) underlying the response to EGCG exposure. EGCG inhibited the in vitro growth of invasive bladder carcinoma cells with an IC(50) range of 70-87 microM. At a concentration of 20 microM, EGCG decreased the migratory potential of bladder carcinoma cells with concomitant activation of p42/44 MAPK and STAT3 and inactivation of Akt. Using biochemical inhibitors of MAPK/ERK, and siRNA to knockdown STAT3 and Akt, inhibition of migration was recorded associated with Akt but not MAPK/ERK or STAT3 signaling in bladder cells. In addition, EGCG downregulated N-cadherin in a dose-dependent manner where reduction in N-cadherin expression paralleled declining migratory potential. Continuous feeding of EGCG to mice prior to and during the establishment of bladder carcinoma xenografts in vivo revealed >50% reduction in mean final tumor volume (P = 0.05) with no detectable toxicity. EGCG inhibited bladder carcinoma cell growth and suppressed the in vitro migration capacity of cells via downregulation of N-cadherin and inactivation of Akt signaling. Continuous administration of EGCG to mice revealed significant inhibition of tumor growth in vivo indicating a possible preventative role for green tea in bladder cancer. 相似文献
999.
Three juvenile narwhals captured during August 1998 in the northeast of Svalbard, Norway, were equipped with satellite-relayed
data loggers (SRDLs) that transmitted diving and swim-speed data, in addition to location, for up to 46 days. A total of 1,354
complete dive cycles were recorded. Most of the diving was shallow and of short duration. Maximum recorded dive depth was
546 m, maximum recorded dive duration was 24.8 min, and maximum recorded swim-speed was 4.7 ms−1. Ascent speed, vertical ascent speed, descent speed and vertical descent speed were all significantly higher during deep
dives (>200 m) than for shallow dives (<200 m). In addition both ascent and descent angles were much steeper for deep dives
than during shallow dives. Most of the shallow diving seemed to be associated with travelling, with the animal shifting between
various locations, while the deep diving (often to the bottom) for extended periods in some specific areas might have been
associated with foraging. Even though the sample size in this study is small, the data are the first information available
for movements and diving behaviour of narwhals near Svalbard. 相似文献
1000.