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101.
102.
Magda Gioia Giovanni Francesco Fasciglione Susanna Monaco Riccardo Iundusi Diego Sbardella Stefano Marini Umberto Tarantino Massimo Coletta 《Journal of biological inorganic chemistry》2010,15(8):1219-1232
The proteolytic processing of collagen I by three matrix metalloproteinases (MMPs), a collagenase (MMP-1), a gelatinase (MMP-2),
and the ectodomain of a membrane-type metalloproteinase (MMP-14), has been investigated at 37 °C between pH 6.0 and 9.2, a
pH range reflecting conditions found in different body compartments under various physiopathological processes. In the proteolytic
degradation the native collagen triple helix must be partially unwound to allow the binding of α chains to the protease’s
active-site cleft. We have found that MMP-1 interacts with the two types of collagen I α chains in a similar fashion, whereas
both MMP-2 and MMP-14 bind the two α chains in a different way. The overall enzymatic activity is higher on the α-2 chain
for both MMP-1 and MMP-2, whereas the MMP-14 ectodomain preferentially cleaves the α-1 chain. In MMP-2 a marked difference
for substrate affinity (higher for the α-1 chain) is overwhelmed by an even more marked propensity to cleave the α-2 chain.
As a whole, the three classes of MMPs investigated appear to process collagen I in a significantly different fashion, so various
MMPs play different roles in the collagen homeostasis in various compartments (such as bloodstream, synovial fluid, normal
and tumoral tissues), where different pH values are observed. 相似文献
103.
Cilurzo F Cupone IE Minghetti P Buratti S Selmin F Gennari CG Montanari L 《AAPS PharmSciTech》2010,11(4):1511-1517
This work aimed to develop a fast-dissolving film made of low dextrose equivalent maltodextrins (MDX) containing nicotine
hydrogen tartrate salt (NHT). Particular attention was given to the selection of the suitable taste-masking agent (TMA) and
the characterisation of the ductility and flexibility under different mechanical stresses. MDX with two different dextrose
equivalents (DEs), namely DE 6 and DE 12, were selected in order to evaluate the effect of polymer molecular weight on film
tensile properties. The bitterness and astringency intensity of NHT and the suppression effect of several TMA were evaluated
by a Taste-Sensing System. The films were characterised in term of NHT content, tensile properties, disintegration time and
drug dissolution test. As expected, placebo films made of MDX DE 6 appeared stiffer and less ductile than film prepared using
MDX DE 12. The films disintegrated within 10 s. Among the tested TMA, the milk and mint flavours resulted particularly suitable
to mask the taste of NHT. The addition of NHT and taste-masking agents affected film tensile properties; however, the effect
of the addition of these components can be counterweighted by modulating the glycerine content and/or the MDX molecular weight.
The feasibility of NHT loaded fast-dissolving films was demonstrated. 相似文献
104.
105.
Among 21 human strains of Laribacter hongkongensis, small plasmids were observed in four strains, and large ones in six strains. The smallest, 3264-bp plasmid, pHLHK19, has only one ORF that encodes a putative replication initiator protein and a predicted origin of replication (ori) with a DnaA box, three 18-bp direct repeats and five pairs of inverted repeats. An Escherichia coli-L. hongkongensis shuttle vector was constructed by ligating the HindIII-digested pHLHK19, containing the replication initiator protein and ori of pHLHK19, to HindIII-digested pBK-CMV. This shuttle vector can propagate in E. coli and L. hongkongensis with good transformation efficiencies. 相似文献
106.
Bertolini LR Bertolini M Anderson GB Maga EA Madden KR Murray JD 《Journal of biotechnology》2007,128(2):246-257
Non-homologous end joining (NHEJ) is the major DNA double-strand break (DSB) repair pathway in mammalian cells and is likely responsible for the non-homologous integration of transgenes. In higher eukaryotes, this pathway predominates over the homologous recombination (HR) pathway and therefore may account for the low level of HR events that occur in mammalian cells. We evaluated the effects of transient RNAi-induced down-regulation of key components of the NHEJ pathway in human HCT116 cells. Treatment with siRNA targeting Ku70 and Xrcc4 reduced corresponding protein levels by 80-90% 48h after transfection, with a return to normal levels by 96h. Additionally, down-regulation of Ku70 and Xrcc4 resulted in a concomitant depletion of both Ku70 and Ku86 proteins. Biological consequences of transient RNAi-mediated depletion of Ku70 and Xrcc4 included sensitization to gamma radiation and a significant decrease in the expression of a linear GFP reporter gene. The results highlight the possibility of a successful means to manipulate the NHEJ pathway by RNAi. 相似文献
107.
Regulation of DMBT1 via NOD2 and TLR4 in intestinal epithelial cells modulates bacterial recognition and invasion 总被引:3,自引:0,他引:3
Rosenstiel P Sina C End C Renner M Lyer S Till A Hellmig S Nikolaus S Fölsch UR Helmke B Autschbach F Schirmacher P Kioschis P Hafner M Poustka A Mollenhauer J Schreiber S 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(12):8203-8211
Mucosal epithelial cell layers are constantly exposed to a complex resident microflora. Deleted in malignant brain tumors 1 (DMBT1) belongs to the group of secreted scavenger receptor cysteine-rich proteins and is considered to be involved in host defense by pathogen binding. This report describes the regulation and function of DMBT1 in intestinal epithelial cells, which form the primary immunological barrier for invading pathogens. We report that intestinal epithelial cells up-regulate DMBT1 upon proinflammatory stimuli (e.g., TNF-alpha, LPS). We demonstrate that DMBT1 is a target gene for the intracellular pathogen receptor NOD2 via NF-kappaB activation. DMBT1 is strongly up-regulated in the inflamed intestinal mucosa of Crohn's disease patients with wild-type, but not with mutant NOD2. We show that DMBT1 inhibits cytoinvasion of Salmonella enterica and LPS- and muramyl dipeptide-induced NF-kappaB activation and cytokine secretion in vitro. Thus, DMBT1 may play an important role in the first line of mucosal defense conferring immune exclusion of bacterial cell wall components. Dysregulated intestinal DMBT1 expression due to mutations in the NOD2/CARD15 gene may be part of the complex pathophysiology of barrier dysfunction in Crohn's disease. 相似文献
108.
Assarsson E Chambers BJ Högstrand K Berntman E Lundmark C Fedorova L Imreh S Grandien A Cardell S Rozell B Ljunggren HG 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(8):5018-5027
Transgenic mice were generated expressing NK1.1, an NK cell-associated receptor, under control of the human CD2 promoter. Unexpectedly, one of the founder lines, Tg66, showed a marked defect in thymic development characterized by disorganized architecture and small size. Mapping of the transgene insertion by fluorescence in situ hybridization revealed integration in chromosome 2, band G. Already from postnatal day 3, the thymic architecture was disturbed with a preferential loss of cortical thymic epithelial cells, a feature that became more pronounced over time. Compared with wild-type mice, total thymic cell numbers decreased dramatically between 10 and 20 days of age. Thymocytes isolated from adult Tg66 mice were predominantly immature double-negative cells, indicating a block in thymic development at an early stage of differentiation. Consequently, Tg66 mice had reduced numbers of peripheral CD4(+) and CD8(+) T cells. Bone marrow from Tg66 mice readily reconstituted thymi of irradiated wild-type as well as RAG-deficient mice. This indicates that the primary defect in Tg66 mice resided in nonhemopoietic stromal cells of the thymus. The phenotype is observed in mice heterozygous for the insertion and does not resemble any known mutations affecting thymic development. Preliminary studies in mice homozygous for transgene insertion reveal a more accelerated and pronounced phenotype suggesting a semidominant effect. The Tg66 mice may serve as a useful model to identify genes regulating thymic epithelial cell differentiation, thymic development, and function. 相似文献
109.
Filipponi D Hobbs RM Ottolenghi S Rossi P Jannini EA Pandolfi PP Dolci S 《Molecular and cellular biology》2007,27(19):6770-6781
110.