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921.
Background
Magnetic stimulation has gained relatively wide application in studying nervous system structures. This technology has the advantage of reduced excitation of sensory nerve endings, and hence results in quasi-painless action. It has become clinically accepted modality for brain stimulation. However, theoretical and practical solutions for assessment of induced current distribution need more detailed and accurate consideration. 相似文献922.
Matrix metalloproteinases are involved in C-terminal and interglobular domain processing of cartilage aggrecan in late stage cartilage degradation. 总被引:13,自引:0,他引:13
Christopher B Little Clare E Hughes Clare L Curtis Mike J Janusz Richard Bohne Sherry Wang-Weigand Yetunde O Taiwo Peter G Mitchell Ivan G Otterness Carl R Flannery Bruce Caterson 《Matrix biology》2002,21(3):271-288
Monoclonal antibody (MAb) technology was used to examine aggrecan metabolites and the role of aggrecanases and matrix metalloproteinases (MMPs) in proteolysis of the interglobular domain (IGD) and C-terminus of aggrecan. An in vitro model of progressive cartilage degradation characterized by early proteoglycan loss and late stage collagen catabolism was evaluated in conjunction with a broad-spectrum inhibitor of MMPs. We have for the first time demonstrated that IGD cleavage by MMPs occurs during this late stage cartilage degeneration, both as a primary event in association with glycosaminoglycan (GAG) release from the tissue and secondarily in trimming of aggrecanase-generated G1 metabolites. Additionally, we have shown that MMPs were responsible for C-terminal catabolism of aggrecan and generation of chondroitin sulfate (CS) deficient aggrecan monomers and that this aggrecan truncation occurred prior to detectable IGD cleavage by MMPs. The onset of this later stage MMP activity was also evident by the generation of MMP-specific link protein catabolites in this model culture system. Recombinant MMP-1, -3 and -13 were all capable of C-terminally truncating aggrecan with at least two cleavage sites N-terminal to the CS attachment domains of aggrecan. Through analysis of aggrecan metabolites in pathological synovial fluids from human, canine and equine sources, we have demonstrated the presence of aggrecan catabolites that appear to have resulted from similar C-terminal processing of aggrecan as that induced in our in vitro culture systems. Finally, by developing a new MAb recognizing a linear epitope in the IGD of aggrecan, we have identified two novel aggrecan metabolites generated by an as yet unidentified proteolytic event. Collectively, these results suggest that C-terminal processing of aggrecan by MMPs may contribute to the depletion of cartilage GAG that leads to loss of tissue function in aging and disease. Furthermore, analysis of aggrecan metabolites resulting from both C-terminal and IGD cleavage by MMPs may prove useful in monitoring different stages in the progression of cartilage degeneration. 相似文献
923.
Potent, orally active inhibitors of lipoprotein-associated phospholipase A(2): 1-(biphenylmethylamidoalkyl)-pyrimidones. 总被引:4,自引:0,他引:4
Helen F Boyd Stephen C M Fell Deirdre M B Hickey Robert J Ife Colin A Leach Colin H Macphee Kevin J Milliner Ivan L Pinto D Anthony Rawlings Stephen A Smith Ian G Stansfield Steven J Stanway Colin J Theobald Caroline M Whittaker 《Bioorganic & medicinal chemistry letters》2002,12(1):51-55
A series of 1-(biphenylmethylamidoalkyl)-pyrimidones has been designed as nanomolar inhibitors of recombinant lipoprotein-associated phospholipase A(2) with high potency in whole human plasma. 5-(Pyrazolylmethyl) derivative 16 and 5-(methoxypyrimidinylmethyl) derivative 27 demonstrated excellent pharmacodynamic profiles which correlated well with their pharmacokinetic effects. 相似文献
924.
Alexei V. Lobanov Ivan A. Borisov Sherald H. Gordon Richard V. Greene Timothy D. Leathers Anatoly N. Reshetilov 《Biosensors & bioelectronics》2001,16(9-12):1001-1007
Although biosensors based on whole microbial cells have many advantages in terms of convenience, cost and durability, a major limitation of these sensors is often their inability to distinguish between different substrates of interest. This paper demonstrates that it is possible to use sensors entirely based upon whole microbial cells to selectively measure ethanol and glucose in mixtures. Amperometric sensors were constructed using immobilized cells of either Gluconobacter oxydans or Pichia methanolica. The bacterial cells of G. oxydans were sensitive to both substrates, while the yeast cells of P. methanolica oxidized only ethanol. Using chemometric principles of polynomial approximation, data from both of these sensors were processed to provide accurate estimates of glucose and ethanol over a concentration range of 1.0–8.0 mM (coefficients of determination, R2=0.99 for ethanol and 0.98 for glucose). When data were processed using an artificial neural network, glucose and ethanol were accurately estimated over a range of 1.0–10.0 mM (R2=0.99 for both substrates). The described methodology extends the sphere of utility for microbial sensors. 相似文献
925.
926.
Gerardo Ivan Zardi Katy Rebecca Nicastro Christopher David McQuaid Marcos Gektidis 《PloS one》2009,4(8)
Biotic stress may operate in concert with physical environmental conditions to limit or facilitate invasion processes while altering competitive interactions between invaders and native species. Here, we examine how endolithic parasitism of an invasive and an indigenous mussel species acts in synergy with abiotic conditions of the habitat. Our results show that the invasive Mytilus galloprovincialis is more infested than the native Perna perna and this difference is probably due to the greater thickness of the protective outer-layer of the shell of the indigenous species. Higher abrasion due to waves on the open coast could account for dissimilarities in degree of infestation between bays and the more wave-exposed open coast. Also micro-scale variations of light affected the level of endolithic parasitism, which was more intense at non-shaded sites. The higher levels of endolithic parasitism in Mytilus mirrored greater mortality rates attributed to parasitism in this species. Condition index, attachment strength and shell strength of both species were negatively affected by the parasites suggesting an energy trade-off between the need to repair the damaged shell and the other physiological parameters. We suggest that, because it has a lower attachment strength and a thinner shell, the invasiveness of M. galloprovincialis will be limited at sun and wave exposed locations where endolithic activity, shell scouring and risk of dislodgement are high. These results underline the crucial role of physical environment in regulating biotic stress, and how these physical-biological interactions may explain site-to-site variability of competitive balances between invasive and indigenous species. 相似文献
927.
Changiz Geula Sara R. Dunlop Ivan Ayala Allegra S. Kawles Margaret E. Flanagan Tamar Gefen Marek-Marsel Mesulam 《Journal of neurochemistry》2021,158(6):1394-1411
928.
Ruben Duran 《Mycopathologia》1971,44(2):89-94
Mating experiments between monosporidial lines ofSorosporium consanguineum from Mexico and the Pacific Northwest indicate that incompatibility in theAristida smut is controlled by multiple alleles at one locus. Alleles a1 a2 were demonstrated in a collection from Chihuahua, Mexico onAristida ternipes. It is hypothesized that these alleles also control incompatibility in collections of the smut from western United States. Alleles a1 a3 were detected in a collection from Durango Mexico onAristida divaricata. Apparently, this is the first time multiple alleles have been shown to control heterothallism inS. consanguineum.Scientific Paper No. 3541. Washington Agricultural Experiment Stations, Pullman, Project 1729. 相似文献
929.
The elongation step of translation is a key contributor to the abundance, folding and quality of proteins and to the stability of mRNA. However, control over translation elongation has not been thoroughly investigated. In this study, a Renilla–firefly luciferase fusion reporter system was further developed to investigate the in vitro elongation rate and processivity of ribosomes independent of the initiation and termination steps. The reporter mRNA was constructed to contain a single ORF encoding in-frame Renilla luciferase, a specific domain moiety and firefly luciferase. Such a reporter structure enables the quantitative and individual evaluation of the synthesis of a specific domain. As a proof of principle, the synthesis of three protein domains of different lengths and structures was analyzed. Using a cell-free translation assay, both the elongation rate and processivity of ribosomes were shown to vary depending on the domain synthesized. Additionally, a stalling sequence consisting of ten rare arginine codons notably reduced the elongation rate and the processivity of the ribosomes. All these results are consistent with the previously known dynamics of elongation in vivo. Overall, the methodology presented in this report provides a framework for studying aspects that contribute to the elongation step of translation. 相似文献
930.