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991.
Paszczynski AJ Paidisetti R Johnson AK Crawford RL Colwell FS Green T Delwiche M Lee H Newby D Brodie EL Conrad M 《Biodegradation》2011,22(6):1045-1059
The Test Area North (TAN) site at the Idaho National Laboratory near Idaho Falls, ID, USA, sits over a trichloroethylene (TCE) contaminant plume in the Snake River Plain fractured basalt aquifer. Past observations have provided evidence that TCE at TAN is being transformed by biological natural attenuation that may be primarily due to co-metabolism in aerobic portions of the plume by methanotrophs. TCE co-metabolism by methanotrophs is the result of the broad substrate specificity of microbial methane monooxygenase which permits non-specific oxidation of TCE in addition to the primary substrate, methane. Arrays of experimental approaches have been utilized to understand the biogeochemical processes driving intrinsic TCE co-metabolism at TAN. In this study, aerobic methanotrophs were enumerated by qPCR using primers targeting conserved regions of the genes pmoA and mmoX encoding subunits of the particulate MMO (pMMO) and soluble MMO (sMMO) enzymes, respectively, as well as the gene mxa encoding the downstream enzyme methanol dehydrogenase. Identification of proteins in planktonic and biofilm samples from TAN was determined using reverse phase ultra-performance liquid chromatography (UPLC) coupled with a quadrupole-time-of-flight (QToF) mass spectrometer to separate and sequence peptides from trypsin digests of the protein extracts. Detection of MMO in unenriched water samples from TAN provides direct evidence of intrinsic methane oxidation and TCE co-metabolic potential of the indigenous microbial population. Mass spectrometry is also well suited for distinguishing which form of MMO is expressed in situ either soluble or particulate. Using this method, pMMO proteins were found to be abundant in samples collected from wells within and adjacent to the TCE plume at TAN. 相似文献
992.
Misztal K Wisniewska MB Ambrozkiewicz M Nagalski A Kuznicki J 《The Journal of biological chemistry》2011,286(36):31781-31788
Nuclear localization of β-catenin is a hallmark of canonical Wnt signaling, a pathway that plays a crucial role in brain development and the neurogenesis of the adult brain. We recently showed that β-catenin accumulates specifically in mature thalamic neurons, where it regulates the expression of the Ca(v)3.1 voltage-gated calcium channel gene. Here, we investigated the mechanisms underlying β-catenin accumulation in thalamic neurons. We report that a lack of soluble factors produced either by glia or cortical neurons does not impair nuclear β-catenin accumulation in thalamic neurons. We next found that the number of thalamic neurons with β-catenin nuclear localization did not change when the Wnt/Dishevelled signaling pathway was inhibited by Dickkopf1 or a dominant negative mutant of Dishevelled3. These results suggest a WNT-independent cell-autonomous mechanism. We found that the protein levels of APC, AXIN1, and GSK3β, components of the β-catenin degradation complex, were lower in the thalamus than in the cortex of the adult rat brain. Reduced levels of these proteins were also observed in cultured thalamic neurons compared with cortical cultures. Finally, pulse-chase experiments confirmed that cytoplasmic β-catenin turnover was slower in thalamic neurons than in cortical neurons. Altogether, our data indicate that the nuclear localization of β-catenin in thalamic neurons is their cell-intrinsic feature, which was WNT-independent but associated with low levels of proteins involved in β-catenin labeling for ubiquitination and subsequent degradation. 相似文献
993.
Andrzej J. W?odarczyk Piotr P. Romańczyk Wojciech Nitek 《Inorganica chimica acta》2011,367(1):217-221
The unusual 18e seven-coordinate Mo(II) complex [Mo(NO)(H2NO-κ2N,O)(TpMe2)I] (1; [TpMe2]− is hydrotris(3,5-dimethylpyrazol-1-yl)borate) has been synthesised and characterised by IR, 1H NMR and ESI-MS spectroscopies and by a single crystal X-ray diffraction study. The complex has a distorted pentagonal bipyramid structure with equatorial κ2-NH2O− ligand (dN-O = 1.387 Å, dMo-N and dMo-O equal 2.049 and 2.092 Å, respectively). In the solid state 1 exists as a dimer (the point group Ci) due to the formation of two NH?O hydrogen bonds (dN-H?O = 2.064 Å) between the adjacent NH2O− ligands, whilst in solution at/or above RT it resolves itself giving a monomer, which readily isomerises to more thermodynamically stable diastereoisomer. 相似文献
994.
995.
Charcot-Marie-Tooth disease 2 is an inherited axonal motor and sensory neuropathy. It is very heterogenous, both clinically and genetically. Till present, 15 types of CMT2, 14 loci and 13 genes are known to be causative of CMT2. Studying mechanisms of molecular pathogenesis is very important for finding a therapy for patients but the diversity of proteins involved in pathogenesis makes this very difficult. Proteins involved in molecular pathogenesis are e.g. proteins of the mitochondrial outer membrane with opposite functions (mitofusin 2 and GDAP1) responsible for fusion and fission of the mitochondrial network. Mutations also occur in genes encoding tRNA-synthetases, neuronal cytoskeletal protein, cation channel protein and molecular chaperones. This review presents knowledge of CMT2 and possible pathogenetic mechanisms responsible for the disease. 相似文献
996.
Leo JC Lyskowski A Hattula K Hartmann MD Schwarz H Butcher SJ Linke D Lupas AN Goldman A 《Structure (London, England : 1993)》2011,19(7):1021-1030
The Escherichia coli Ig-binding (Eib) proteins are trimeric autotransporter adhesins (TAAs) and receptors for IgG Fc. We present the structure of a large fragment of the passenger domain of EibD, the first TAA structure to have both a YadA-like head domain and the entire coiled-coil stalk. The stalk begins as a right-handed superhelix, but switches handedness halfway down. An unexpected β-minidomain joins the two and inserts a ~120° rotation such that there is no net twist between the beginning and end of the stalk. This may be important in folding and autotransport. The surprisingly large cavities we found in EibD and other TAAs may explain how TAAs bend to bind their ligands. We identified how IgA and IgG bind and modeled the EibD-IgG Fc complex. We further show that EibD promotes autoagglutination and biofilm formation and forms a fibrillar layer covering the cell surface making zipper-like contacts between cells. 相似文献
997.
Lipid rafts constitute dynamic assemblies within a bilayer, engaged in, e.g., signal transduction, membrane trafficking and cell polarization. Despite wide interest in the process of domain formation in binary or ternary lipid model systems, only a limited number of papers are devoted to the influence of different additives on this process. In particular, works devoted to the role of drugs in raft formation are missing. In the present study, the influence of trifluoperazine, thioridazine and chlorpromazine on domain organization in raft-mimicking model membranes was investigated. Using giant unilamellar vesicles formed from an equimolar DOPC:sphingomyelin:cholesterol mixture, we found that phenothiazines elevated the number of domains, decreased their area and markedly increased the total length of the domain border. The impact of studied drugs on phase separation in the raft lipid mixture was also confirmed by Laurdan generalized polarization measurements. Alteration of domain organization induced by antipsychotic drugs was very likely to arise from selective accumulation of phenothiazines in interfacial regions between liquid ordered and liquid disordered domains. Interpretation of the results allowed us to demonstrate new aspects underlaying mechanisms of action of phenothiazine-type antipsychotic drugs. To the best of our knowledge, this is the first report demonstrating the influence of drugs on domain morphology directly visualized in giant unilamellar vesicles. 相似文献
998.
Milena Saqui-Salces Evelyn Covés-Datson Natalia A. Veniaminova Meghna Waghray Li-Jyun Syu Andrzej A. Dlugosz Juanita L. Merchant 《PloS one》2012,7(10)
Chronic inflammation in the stomach can lead to gastric cancer. We previously reported that gastrin-deficient (Gast−/−) mice develop bacterial overgrowth, inflammatory infiltrate, increased Il-1β expression, antral hyperplasia and eventually antral tumors. Since Hedgehog (Hh) signaling is active in gastric cancers but its role in precursor lesions is poorly understood, we examined the role of inflammation and Hh signaling in antral hyperplasia. LacZ reporter mice for Sonic hedgehog (Shh), Gli1, and Gli2 expression bred onto the Gast−/− background revealed reduced Shh and Gli1 expression in the antra compared to wild type controls (WT). Gli2 expression in the Gast−/− corpus was unchanged. However in the hyperplastic Gast−/− antra, Gli2 expression increased in both the mesenchyme and epithelium, whereas expression in WT mice remained exclusively mesenchymal. These observations suggested that Gli2 is differentially regulated in the hyperplastic Gast−/− antrum versus the corpus and by a Shh ligand-independent mechanism. Moreover, the proinflammatory cytokines Il-1β and Il-11, which promote gastric epithelial proliferation, were increased in the Gast−/− stomach along with Infγ. To test if inflammation could account for elevated epithelial Gli2 expression in the Gast−/− antra, the human gastric cell line AGS was treated with IL-1β and was found to increase GLI2 but decrease GLI1 levels. IL-1β also repressed human GAST gene expression. Indeed, GLI2 but not GLI1 or GLI3 expression repressed gastrin luciferase reporter activity by ∼50 percent. Moreover, chromatin immunoprecipitation of GLI2 in AGS cells confirmed that GLI2 directly binds to the GAST promoter. Using a mouse model of constitutively active epithelial GLI2 expression, we found that activated GLI2 repressed Gast expression but induced Il-1β gene expression and proliferation in the gastric antrum, along with a reduction of the number of G-cells. In summary, epithelial Gli2 expression was sufficient to stimulate Il-1β expression, repress Gast gene expression and increase proliferation, leading to antral hyperplasia. 相似文献
999.
X-ray evidence for metal–N-7 bonding in a hydrated manganese derivative of guanosine 5′-monophosphate (Short Communication) 下载免费PDF全文
Patrice de Meester David M. L. Goodgame T. Jeffrey Jones Andrzej C. Skapski 《The Biochemical journal》1974,139(3):791-792
Single-crystal X-ray studies of a manganese(II) derivative of guanosine 5'-monophosphate, [Mn(5'-GMP)(H(2)O)(5)],3H(2)O, have shown that it is isostructural with its nickel analogue. The manganese atom therefore is bonded to five water molecules with the remaining octahedral co-ordination site being occupied by N-7 of the nucleotide base. No direct metal-phosphate bonding is involved, but there are structure-stabilizing intramolecular hydrogen bonds between two phosphate oxygen atoms and co-ordinated water molecules. 相似文献
1000.
Synthetic analogs of vitamin D for potential use in differentiation therapy should selectively regulate genes necessary for differentiation without inducing any perturbations in calcium homeostasis. PRI-1906, an analog of vitamin D2, and PRI-2191, an analog of vitamin D3 bind nuclear vitamin D receptor (nVDR) with substantially lower affinity than 1,25-dihydroxyvitamin D3 (1,25-D3), but have higher differentiation-inducing activity as estimated in HL-60 leukemia cellmodel. To examine how their increased differentiation-inducing activity is regulated we tested the hypothesis that membrane-mediated events, unrelated to nVDR, take part in the differentiation in response to PRI-1906 and PRI-2191. The induction of leukemia cell differentiation in response to the analogs of vitamin D was inhibited by LY294002 (phosphatidylinositol 3-kinase inhibitor), PD98059 (inhibitor of MEK1,2, an upstream regulator of extracellular-signal regulated kinase) and rapamycin (p70S6K inhibitor) pointing out that activation of signal transduction pathways unrelated to nVDR is necessary for differentiation. On the other hand, inhibition of cytosolic phospholipase A2 accelerated the differentiation of HL-60 cells induced by either 1,25-D3 or by the vitamin D analogs suggesting possible existence of a feedback loop between extracellular-signal regulated kinases and phospholipase A2. 相似文献