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991.
Woo JA Jung AR Lakshmana MK Bedrossian A Lim Y Bu JH Park SA Koo EH Mook-Jung I Kang DE 《Cell death and differentiation》2012,19(9):1413-1423
Neurodegeneration associated with amyloid β (Aβ) peptide accumulation, synaptic loss, neuroinflammation, tauopathy, and memory impairments encompass the pathophysiological features of Alzheimer's disease (AD). We previously reported that the scaffolding protein RanBP9, which is overall increased in brains of AD patients, simultaneously promotes Aβ generation and focal adhesion disruption by accelerating the endocytosis of amyloid precursor protein (APP) and β1-integrin, respectively. Here, we show that RanBP9 protein levels are increased by fourfold in FAD mutant APP transgenic mice. Accordingly, RanBP9 transgenic mice demonstrate significantly increased synapse loss, neurodegeneration, gliosis, and spatial memory deficits. RanBP9 overexpression promotes apoptosis and potentiates Aβ-induced neurotoxicity independent of its capacity to promote Aβ generation. Conversely, RanBP9 reduction by siRNA or gene dosage mitigates Aβ-induced neurotoxicity. Importantly, RanBP9 activates/dephosphorylates cofilin, a key regulator of actin dynamics and mitochondria-mediated apoptosis, and siRNA knockdown of cofilin abolishes both Aβ and RanBP9-induced apoptosis. These findings implicate the RanBP9-cofilin pathway as critical therapeutic targets not only for stemming Aβ generation but also antagonizing Aβ-induced neurotoxicity. 相似文献
992.
In wireless sensor networks, when a sensor node detects events in the surrounding environment, the sensing period for learning
detailed information is likely to be short. However, the short sensing cycle increases the data traffic of the sensor nodes
in a routing path. Since the high traffic load causes a data queue overflow in the sensor nodes, important information about
urgent events could be lost. In addition, since the battery energy of the sensor nodes is quickly exhausted, the entire lifetime
of wireless sensor networks would be shortened. In this paper, to address these problem issues, a new routing protocol is
proposed based on a lightweight genetic algorithm. In the proposed method, the sensor nodes are aware of the data traffic
rate to monitor the network congestion. In addition, the fitness function is designed from both the average and the standard
deviation of the traffic rates of sensor nodes. Based on dominant gene sets in a genetic algorithm, the proposed method selects
suitable data forwarding sensor nodes to avoid heavy traffic congestion. In experiments, the proposed method demonstrates
efficient data transmission due to much less queue overflow and supports fair data transmission for all sensor nodes. From
the results, it is evident that the proposed method not only enhances the reliability of data transmission but also distributes
the energy consumption across wireless sensor networks. 相似文献
993.
Jiahn-Dar HuangJuan Amaral Jung Wha LeeIgnacio M. Larrayoz Ignacio R. Rodriguez 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2012,1821(4):637-646
Sterculic acid is a cyclopropene fatty acid with numerous biological activities. In this study we demonstrate that sterculic acid is a potent inhibitor of endoplasmic reticulum (ER) stress and related inflammation caused by 7-ketocholesterol (7KCh). 7KCh is a highly toxic oxysterol suspected in the pathogenesis of various age-related diseases such as atherosclerosis, Alzheimer's disease and age-related macular degeneration. Sterculic acid demonstrated to be 5-10 times more effective than other anti-inflammatory fatty acids at inhibiting 7KCh-mediated inflammatory responses in cultured cells. In vivo, sterculic acid was effective at inhibiting the formation of choroidal neovascularization (CNV) in the laser-injury rat model. Our data suggests that sterculic acid may be useful in treating CNV in certain forms of age-related macular degeneration. 相似文献
994.
In the cyanobacterium Synechocystis sp PCC 6803, early steps in thylakoid membrane (TM) biogenesis are considered to take place in specialized membrane fractions resembling an interface between the plasma membrane (PM) and TM. This region (the PratA-defined membrane) is defined by the presence of the photosystem II (PSII) assembly factor PratA (for processing-associated TPR protein) and the precursor of the D1 protein (pD1). Here, we show that PratA is a Mn(2+) binding protein that contains a high affinity Mn(2+) binding site (K(d) = 73 μM) and that PratA is required for efficient delivery of Mn(2+) to PSII in vivo, as Mn(2+) transport is retarded in pratA(-). Furthermore, ultrastructural analyses of pratA(-) depict changes in membrane organization in comparison to the wild type, especially a semicircle-shaped structure, which appears to connect PM and TM, is lacking in pratA(-). Immunogold labeling located PratA and pD1 to these distinct regions at the cell periphery. Thus, PratA is necessary for efficient delivery of Mn(2+) to PSII, leading to Mn(2+) preloading of PSII in the periplasm. We propose an extended model for the spatial organization of Mn(2+) transport to PSII, which is suggested to take place concomitantly with early steps of PSII assembly in biogenesis centers at the cell periphery. 相似文献
995.
The DJ-1 superfamily (DJ-1/ThiJ/PfpI superfamily) is distributed across all three kingdoms of life. These proteins are involved
in a highly diverse range of cellular functions, including chaperone and protease activity. DJ-1 proteins usually form dimers
or hexamers in vivo and show at least four different binding orientations via distinct interface patches. Abnormal oligomerization of human DJ-1 is related to neurodegenerative disorders including Parkinson’s
disease, suggesting important functional roles of quaternary structures. However, the quaternary structures of the DJ-1 superfamily
have not been extensively studied. Here, we focus on the diverse oligomerization modes among the DJ-1 superfamily proteins
and investigate the functional roles of quaternary structures both computationally and experimentally. The oligomerization
modes are classified into 4 types (DJ-1, YhbO, Hsp, and YDR types) depending on the distinct interface patches (I-IV) upon
dimerization. A unique, rotated interface via patch I is reported, which may potentially be related to higher order oligomerization.
In general, the groups based on sequence similarity are consistent with the quaternary structural classes, but their biochemical
functions cannot be directly inferred using sequence information alone. The observed phyletic pattern suggests the dynamic
nature of quaternary structures in the course of evolution. The amino acid residues at the interfaces tend to show lower mutation
rates than those of non-interfacial surfaces. 相似文献
996.
Choi HR Kim WK Kim EY Jung H Kim JH Han BS You KH Lee SC Bae KH 《Journal of microbiology and biotechnology》2012,22(7):1029-1033
A number of evidence have been accumulated that the regulation of reversible tyrosine phosphorylation, which can be regulated by the combinatorial activity of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs), plays crucial roles in various biological processes including differentiation. There are a total of 107 PTP genes in the human genome, collectively referred to as the "PTPome." In this study, we performed PTP profiling analysis of the HIB-1B cell line, a brown preadipocyte cell line, during brown adipogenesis. Through RT-PCR and real-time PCR, several PTPs showing differential expression pattern during brown adipogenesis were identified. In the case of PTP-RE, it was shown to decrease significantly until 4 days after brown adipogenic differentiation, followed by a dramatic increase at 6 days. The overexpression of PTP-RE led to decreased brown adipogenic differentiation via reducing the tyrosine phosphorylation of the insulin receptor, indicating that PTP-RE functions as a negative regulator at the early stage of brown adipogenesis. 相似文献
997.
HJ Choi SM Lee SH Kim DW Kim YW Choi WH Joo 《Journal of microbiology and biotechnology》2012,22(9):1214-1217
One Helicosporium strain, isolated from a wilted chestnut tree, evidenced in vitro antimicrobial activity against various types of bacteria and fungi, and generated a diffusible pigment. The antimicrobial compounds and the diffusible pigment of the Helicosporium sp. isolate were purified via solvent fractionation, column chromatography, and recycling preparative chromatography. Both the major antimicrobial compound and the diffusible pigment were identified as 2-methylresorcinol via nuclear magnetic resonance spectroscopy. Therefore, 2-methylresorcinol, a diffusible pigment generated by Helicosporium sp., appears to be an active antimicrobial principle. This pigment also exhibited considerable cytotoxicity against mammalian cells. 相似文献
998.
Nam HJ Kang JK Chang JS Lee MS Nam ST Jung HW Kim SK Ha EM Seok H Son SW Park YJ Kim H 《Journal of microbiology and biotechnology》2012,22(1):50-57
Phospholipase C-γl (PLC-γl) expression is associated with cellular transformation. Notably, PLC-gamma is up-regulated in colorectal cancer tissue and breast carcinoma. Because exotoxins released by Clostridium botulinum have been shown to induce apoptosis and promote growth arrest in various cancer cell lines, we examined here the potential of Clostridium difficile toxin A to selectively induce apoptosis in cells transformed by PLC-γl overexpression. We found that PLC-γl-transformed cells, but not vectortransformed (control) cells, were highly sensitive to C. difficile toxin A-induced apoptosis and mitotic inhibition. Moreover, expression of the proapoptotic Bcl2 family member, Bim, and activation of caspase-3 were significantly up-regulated by toxin A in PLC-γl-transformed cells. Toxin A-induced cell rounding and paxillin dephosphorylation were also significantly higher in PLC-γl-transformed cells than in control cells. These findings suggest that C. difficile toxin A may have potential as an anticancer agent against colorectal cancers and breast carcinomas in which PLC-γl is highly up-regulated. 相似文献
999.
1,2-Dibromoethane and glycidol are well known genotoxic carcinogens, which have been widely used in industry. To identify
a specific biomarker for these carcinogens in cells, the cellular proteome of L5178Y mouse lymphoma cells treated with these
compounds was analyzed by 2-dimensional gel electrophoresis (2-DE) and MALDI-TOF mass spectrometry (MS). Of 50 protein spots
showing a greater than 1.5-fold increase or decrease in intensity compared to control cells on a 2-D gel, we focused on the
candidate biomarker moesin. Western analysis using monoclonal rabbit anti-moesin confirmed the identity of the protein and
its increased level of expression upon exposure to the carcinogenic compounds. Moesin expression also increased in cells treated
with six additional genotoxic carcinogens, verifying that moesin could serve as a biomarker to monitor phenotypic change upon
exposure to genotoxic carcinogens in L5178Y mouse lymphoma cells. 相似文献
1000.
We studied the role of a RhoA-specific guanine nucleotide exchange factor (p190RhoGEF) in dendritic cells (DCs), using transgenic (TG) mice that over-express a full gene of p190RhoGEF under the control of an invariant chain promoter. TG mice lacked localization of activated DCs to the T cell zone in the spleen and had reduced serum levels of IL-6 in response to lipopolysaccharide (LPS) injection. DCs from these mice also showed reduced surface expression of CD86, CD40, and CD205, but not MHCII, as well as a reduced capability to uptake antigen. Moreover, chemokine-driven migration and secretion of IL-6, but not of IL-12, were impaired after LPS-stimulation of TG DCs. Collectively, these results suggest that over-expressing p190RhoGEF negatively regulates conventional DC function in response to bacterial LPS infection. 相似文献