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1.
J. Dierschke T. Krüger F. Hüttmann F. Bairlein Kerstin Müller G. Scheiffarth H. -W. Helb W. Irsch W. Lantermann B. Haubitz W. Winkel und J. Haffer 《Journal of Ornithology》2003,144(4):484-498
Ohne Zusammenfassung 相似文献
2.
Anna Nilsson Thomas E. Fehniger Lena Gustavsson Malin Andersson Kerstin Kenne Gy?rgy Marko-Varga Per E. Andrén 《PloS one》2010,5(7)
Readouts that define the physiological distributions of drugs in tissues are an unmet challenge and at best imprecise, but are needed in order to understand both the pharmacokinetic and pharmacodynamic properties associated with efficacy. Here we demonstrate that it is feasible to follow the in vivo transport of unlabeled drugs within specific organ and tissue compartments on a platform that applies MALDI imaging mass spectrometry to tissue sections characterized with high definition histology. We have tracked and quantified the distribution of an inhaled reference compound, tiotropium, within the lungs of dosed rats, using systematic point by point MS and MS/MS sampling at 200 µm intervals. By comparing drug ion distribution patterns in adjacent tissue sections, we observed that within 15 min following exposure, tiotropium parent MS ions (mass-to-charge; m/z 392.1) and fragmented daughter MS/MS ions (m/z 170.1 and 152.1) were dispersed in a concentration gradient (80 fmol-5 pmol) away from the central airways into the lung parenchyma and pleura. These drug levels agreed well with amounts detected in lung compartments by chemical extraction. Moreover, the simultaneous global definition of molecular ion signatures localized within 2-D tissue space provides accurate assignment of ion identities within histological landmarks, providing context to dynamic biological processes occurring at sites of drug presence. Our results highlight an important emerging technology allowing specific high resolution identification of unlabeled drugs at sites of in vivo uptake and retention. 相似文献
3.
Calcium and the mechanism of axoplasmic transport 总被引:2,自引:0,他引:2
S Ochs 《Federation proceedings》1982,41(7):2301-2306
Using desheathed cat peroneal nerves in in vitro studies, Ca2+ was recently shown to be required to maintain axoplasmic transport. Calmodulin was also shown to be present in nerve and to participate in transport. These findings open up new possibilities for a better understanding of the underlying mechanism of transport. In the transport filament model, the materials transported are bound to a common carrier, the transport filaments, which are moved along the microtubules by means of an interaction with the side arms of the microtubules. This is an energy-requiring process that depends on a supply of ATP, which is utilized by the Ca2+,Mg2+-ATPase associated with the side arms of the microtubules. The Ca2+,Mg2+-ATPase is activated by calmodulin at the low micromolar levels of free Ca2+ present in the axon. The level is kept low by calcium-regulatory mechanisms that include mitochondria, endoplasmic reticulum, and calcium-binding proteins. Nerves exposed to higher-than-normal concentrations of Ca2+ in the medium show an increased number of particles in these organelles as expected of their Ca2+-regulatory role. The nature of the calmodulin-Ca,Mg-ATPase complex associated with the side arms is discussed on the basis of the transport model. Also discussed is slow transport, which is explained on the basis of the model as a differential binding affinity to the transport filaments. 相似文献
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The three potent antimitotic vinca alkaloids: vincristine (VCR), vinblastine (VLB), and vindesine (VDS) were compared for their effect in blocking axoplasmic transport in vitro using a desheathed preparation of the peroneal branch of cat sciatic nerve. A range of vinca alkaloid concentrations from 1–100μM was examined. The relative order of potency in blocking axoplasmic transport was VCR > VLB > VDS at a concentration of 25μM. At the higher concentrations block occurred so rapidly that a statistically significant difference between these agents could not be obtained. The relation of vinca block ot the transport mechanism is discussed. 相似文献
8.
Lars Svennerholm Pam Fredman Birgitta Jungbjer Jan-Eric Månsson Britt-Marie Rynmark Kerstin Boström Bengt Hagberg Lars Norén Pirkko Santavuori 《Journal of neurochemistry》1987,49(6):1772-1783
Lipid composition was studied on cerebral tissue from nine children who had died of a progressive encephalopathy called the infantile form of neuronal ceroid lipofuscinosis (INCL) or polyunsaturated fatty acid lipidosis (PFAL). In the terminal stage of the disease, the concentrations of all lipid classes were found to be significantly reduced in the cerebral and cerebellar cortex and white matter. The concentration of gangliosides of the cerebral cortex was 15% and that of cerebrosides (galactosylceramide) in white matter 0.2-5% of the normal values for the children's ages. The reduction of gangliosides mainly affected those of the gangliotetraose series, particularly GD1a. The fatty acids of the linolenic acid series were strongly reduced in ethanolamine and serine phosphoglycerides. A very large increase up to 100-fold of oligoglycosphingolipids of the globo series and two fucose-containing lipids of the neolacto series was found in the forebrain of the three advanced cases examined. The brain tissue also contained very high concentrations of mono-, di-, and trisialogangliosides of the lacto and neolacto series, gangliosides with type 1 chain dominating. The structures of the gangliosides were tentatively identified by gas chromatography-mass spectrometry and monoclonal antibodies with carefully determined epitope specificity. The gangliosides and neutral glycosphingolipids had very similar fatty acid composition, consisting of about 40% stearic acid and 40% C24-acids. 相似文献
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Cleavage of a hydrophilic C-terminal domain increases growth-inhibitory activity of oncostatin M. 总被引:4,自引:1,他引:3 下载免费PDF全文
Oncostatin M is a polypeptide cytokine, produced by normal and malignant hematopoietic cells, that has several in vitro activities, including the ability to inhibit growth of cultured carcinoma cells. Here we present a structural and functional comparison of two oncostatin M-related proteins (Mr 36,000 and 32,000) secreted by COS cells transfected with oncostatin M cDNA. The smaller of these forms lacked a hydrophilic C-terminal domain comprising predominantly basic amino acids. This domain was also absent from native oncostatin M produced by U937 cells. The 32,000-Mr form of oncostatin M was not produced by cells transfected with plasmids (G195 and G196) in which a potential trypsinlike cleavage site within the hydrophilic C-terminal domain was altered by site-directed mutagenesis. A 32,000-Mr fragment was produced by trypsin treatment of the 36,000-Mr form of oncostatin M. These observations suggest that the 32,000-Mr form of oncostatin M was derived from the 227-amino-acid propeptide by proteolytic cleavage at or near the paired basic residues at positions 195 and 196. Pro-oncostatin M was equally active in radioreceptor assays as the processed form but was 5- to 60-fold less active in growth inhibition assays. Likewise, nonprocessed mutant protein encoded by plasmid G196 was equally active in the radioreceptor assays as the processed form but was five- to ninefold less active in growth inhibition assays. Thus, the highly charged C-terminal domain of pro-oncostatin M is not required for receptor binding or growth-inhibitory activity but may alter the functional properties of the molecule. Propeptide processing of oncostatin M may be important for regulating in vivo activities of this cytokine. 相似文献