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41.
Syed SD Deepak M Yogisha S Chandrashekar AP Muddarachappa KA D'Souza P Agarwal A Venkataraman BV 《Phytotherapy research : PTR》2003,17(4):420-421
Wedelolactone (WL) and demethylwedelolactone (DWL) isolated from Eclipta alba were tested in the trypsin inhibition bioassay (in vitro). Both compounds showed potent activity. IC(50) values of WL and DWL were found to be 2.9 and 3.0 microg/mL respectively. 相似文献
42.
When mast cells are activated, e.g. during allergic responses, they secrete the serine proteases chymase and tryptase, which both are complex-bound to heparin proteoglycan in vivo. Previous reports have demonstrated potent pro-inflammatory effects of both tryptase and chymase in different animal models, suggesting that these serine proteases may be relevant targets for therapeutic intervention. Recent investigations have shown that heparin-binding compounds can cause tryptase inhibition and it has been suggested that the inhibitory activity of such compounds is due to interference with the binding of heparin to tryptase. Here we tested various polycationic peptides for their ability to inhibit heparin-free human recombinant betaI-tryptase. We demonstrate powerful direct inhibition of tryptase (IC(50) values approximately 1-100 nM) by poly-Arg and poly-Lys of different molecular weights. Poly-Arg and poly-Lys showed predominantly competitive inhibition kinetics, although decreases in the k(cat) values for the chromogenic substrate S-2288 were also observed. Peptides built up from heparin-binding motifs were also inhibitors of tryptase, albeit of lower efficiency than poly-Arg/Lys. Tryptase inhibition was strongly dependent on the size of the polycationic peptides. The various polycationic peptides were also inhibitory for heparin-dependent activities of chymase. The tryptase inhibition caused by the polycationic peptides could be reversed by adding heparin. After heparin-induced rescue of tryptase activity, the major part of the tryptase activity was sensitive to inhibition by bovine pancreatic trypsin inhibitor, whereas tryptase before addition of polycationic peptide was completely resistant. Taken together, our findings indicate that polycationic peptides can be used as powerful agents for combined inhibition of mast cell tryptase and chymase. 相似文献
43.
Maria G. Antoniou Jody A. Shoemaker Armah A. de la Cruz Dionysios D. Dionysiou 《Toxicon》2008,51(6):1103-1118
Microcystin-LR (MC-LR), a cyanotoxin and emerging drinking water contaminant, was treated with TiO2 photocatalysts immobilized on stainless steel plates as an alternative to nanoparticles in slurry. The reaction intermediates of MC-LR were identified with mass spectrometry (MS) at pH of Milli-Q water (pHsq=5.7). Eleven new [M+H]+ were observed in the liquid chromatography mass spectrometry (LC/MS) chromatogram with some of them giving multiple peaks. Most of these reaction intermediates have not been reported from previous studies employing TiO2 nanoparticles at acidic conditions (pH=4.0). Investigating the effects of pH (for 3.02 photocatalytic films showed that acidic conditions are preferable for the degradation. Combined with the limited surface area of the films and the absence of additional oxidants (i.e., H2O2) the degradation was slower and more intermediate steps were identified. Possible structures of the intermediates (formed at neutral pH) after analyzing the corresponding MS/MS spectra are reported. The collision-induced dissociation of the [M+H]+ of MC-LR and the intermediates 1011.5 and 1029.5 are discussed and possible fragmentation pathways and mechanisms are also proposed. Analysis of the MS/MS spectra indicates that the fragmentation of some amino acids is less favorable because of internal interaction with free groups of adjacent amino acids. The MS/MS spectra assisted in determining hydroxylation sites, by the formation or alteration of specific product ions such as m/z 599. 相似文献
44.
N. O. BERG S. BORULF I. JAKOBSSON T. LINDBERG 《Acta paediatrica (Oslo, Norway : 1992)》1978,67(4):403-411
ABSTRACT. 180 children (mean age 20 months) suspected of malabsorption because of failure to thrive, abnormal stools more than 3 weeks, vomiting, an/or abdominal distension were investigated with peroral small intestinal biopsy at duodeno-jejunal flexure (172 children) and/or duodenal intubation for analysis of trypsin and amylase activity in duodenal juice before and after a test meal of water (76 children). Results of xylose tolerance test, lactose tolerance test, faecal fat, B-folate, S-iron, and S-albumin were related to morphology of mucosa. A normal finding of one of these tests means in 15–26% a normal mucosa (diagnostic sensitivity). An abnormal finding means in 40–85% a severely damaged mucosa and in 85–100% a slightly, moderately, or severely damaged mucosa (diagnostic specificity). Combinations of these tests increase the diagnostic sensitivity 10–15%. Faecal chymotrypsin seems to be a reliable screening test for exocrine pancreatic function. Border values or low values indicate a direct evaluation of exocrine pancreatic function. The simple test meal (water) method with determination of trypsin in duodenal juice gives, from a practical point of view, good information of the exocrine pancreatic function.
The following plan of investigation is proposed: Step 1. careful clinical history and examination; Step 2. analysis of faeces for Giardia lamblia, entero-pathogenic microorganisms, and chymotrypsin, sweat test; Step 3. peroral small intestinal biopsy and/or duodenal juice analysis, and finally—if steps 2 and 3 give normal results; Step 4. re-evaluation of dietary history and tests to detect any food intolerance (e.g. carbohydrate). 相似文献
The following plan of investigation is proposed: Step 1. careful clinical history and examination; Step 2. analysis of faeces for Giardia lamblia, entero-pathogenic microorganisms, and chymotrypsin, sweat test; Step 3. peroral small intestinal biopsy and/or duodenal juice analysis, and finally—if steps 2 and 3 give normal results; Step 4. re-evaluation of dietary history and tests to detect any food intolerance (e.g. carbohydrate). 相似文献
45.
Age-related changes in the bovine lens trypsin inhibitor activity were measured by assaying water soluble extracts of 10 concentric slices from the periphery to the center of the lens. Inhibitor assays were carried out at pH 7.0 and 7.9 using prenatal, calf and mature lenses. The inhibitor at pH 7.0 remained constant throughout the lens but the pH 7.9 activity decreased sharply in the lens nucleus. This was particularly true for the prenatal and calf lenses. Agarose A-15 m gel filtration of the water soluble inhibitor activity showed a decrease in inhibitor in the alpha-crystallin region and a corresponding increase in inhibitor activity in the HMW protein peak. Inhibitor assays were carried out on the water insoluble fractions following solubilization in 6.0 M-urea. Little or no inhibitor activity was seen in the outer cortical fractions but the inner cortex and nucleus contained high levels of inhibitor activity in the water insoluble fraction with specific activities 7- to 10-fold higher than the comparable crude lens extracts. These data suggest that the lens inhibitor activity at pH 7.0 and 7.9 aggregate into a HMW complex and with time preferentially enter the water insoluble fraction. The distribution of a purified 5.5 K inhibitor protein between the water soluble and the water insoluble fraction was measured. In the periphery all of this inhibitor was in the water soluble fraction, but toward the center of the lens this inhibitor began shifting to the water insoluble fraction. Slices taken from the lens nuclear region showed that all the inhibitor was in the water insoluble fraction as detected by both activity measurements and SDS-PAGE. 相似文献
46.
Christine L. Hvas Christian Fenger-Eriksen Søren Høyer Benny Sørensen Else Tønnesen 《Thrombosis research》2013
Background
Cerebral injury and brain death is associated with apparent hypercoagulation and poor organ outcome. This experimental study challenges the hypotheses that i) brain death causes hypercoagulation and microvascular thrombosis and that ii) neutralizing systemic tissue factor (TF) by in vitro addition of a TF inhibitor (recombinant active site-inhibited factor VIIa (ASIS)) can reverse the hypercoagulable profile.Methods
Using a validated pig model of intracranial hemorrhage and brain death, 20 pigs were randomized to either control or brain death. The primary endpoints were coagulation parameters measured with whole blood thromboelastometry (ROTEM), thrombin generation and a porcine TF-sensitive plasma clotting time assay. In vitro spiking experiments with ASIS were performed in parallel with the latter two assessments. The kidneys were examined histologically for microvascular thromboses.Results
Brain death induced hypercoagulation, as demonstrated with ROTEM, thrombin generation, and reduced TF-sensitive plasma clotting time. In vitro inhibition of TF with ASIS did not reverse the hypercoagulation. No microvascular thromboses were found in the kidneys.Conclusion
Brain death causes hypercoagulation; however, inhibition of TF does not reverse the coagulopathy. Thus, TF release does not seem to be the primary cause of this hypercoagulation. Minor changes in the levels of protein C suggest that the protein C pathway may be linked to the observed coagulopathy. 相似文献47.
Abstract: Native chemical ligation has proven to be a powerful method for the synthesis of small proteins and the semisynthesis of larger ones. The essential synthetic intermediates, which are C‐terminal peptide thioesters, cannot survive the repetitive piperidine deprotection steps of Nα‐9‐fluorenylmethoxycarbonyl (Fmoc) chemistry. Therefore, peptide scientists who prefer to not use Nα‐t‐butyloxycarbonyl (Boc) chemistry need to adopt more esoteric strategies and tactics in order to integrate ligation approaches with Fmoc chemistry. In the present work, side‐chain and backbone anchoring strategies have been used to prepare the required suitably (partially) protected and/or activated peptide intermediates spanning the length of bovine pancreatic trypsin inhibitor (BPTI). Three separate strategies for managing the critical N‐terminal cysteine residue have been developed: (i) incorporation of Nα‐9‐fluorenylmethoxycarbonyl‐S‐(N‐methyl‐N‐phenylcarbamoyl)sulfenylcysteine [Fmoc‐Cys(Snm)‐OH], allowing creation of an otherwise fully protected resin‐bound intermediate with N‐terminal free Cys; (ii) incorporation of Nα‐9‐fluorenylmethoxycarbonyl‐S‐triphenylmethylcysteine [Fmoc‐Cys(Trt)‐OH], generating a stable Fmoc‐Cys(H)‐peptide upon acidolytic cleavage; and (iii) incorporation of Nα‐t‐butyloxycarbonyl‐S‐fluorenylmethylcysteine [Boc‐Cys(Fm)‐OH], generating a stable H‐Cys(Fm)‐peptide upon cleavage. In separate stages of these strategies, thioesters are established at the C‐termini by selective deprotection and coupling steps carried out while peptides remain bound to the supports. Pilot native chemical ligations were pursued directly on‐resin, as well as in solution after cleavage/purification. 相似文献
48.
人尿激肽释放酶和人尿胰蛋白酶抑制剂是存在于尿中的酸性蛋白.本文通过ZnCl2胶体沉淀和乙醇沉淀相结合的方法可有效分离两者,得率高、活性保留好. 相似文献
49.
In the present experiment we used immobilized progesterone linked to bovine serum albumin (P4-3-BSA) as a probe to examine whether the effects of a direct in vitro infusion of progesterone upon dopamine (DA) release from corpus striatal (CS) tissue fragments from ovariectomized estrogen-treated rats may be attributable to a surface membrane site of action. In Expt. I, a direct in vitro pulsatile infusion of P4-3-BSA resulted in two discrete episodes of stimulated DA release which were not observed in superfusions receiving a continuous infusion of P4-3-BSA or compared to data of control superfusions. In contrast to that of a pulsatile administration, a continuous infusion of P4-3-BSA completely abolished the amphetamine-stimulated response from these tissue preparations with significantly lower DA release rates compared to the pulsatile P4-3-BSA (P less than 0.02) and control (P less than 0.04) conditions. In Expt. II, the addition of tetrodotoxin (TTX, 1 microM) to the superfusion medium abolished the discriminatory response between pulsatile and continuous administration of immobilized progesterone. These results indicate that the action of progesterone on DA release from the CS is mediated primarily through a surface membrane site of an interneuron(s) which can discriminately respond to a specific infusion mode of this steroid. 相似文献
50.
†L. Darnige †C. Legallais ‡J. Arvieux †O. Pitiot †M.A. Vijayalakshmi 《Artificial organs》1999,23(9):834-839
It is of considerable interest to ascertain whether a hollow fiber cartridge containing histidine immobilized on polyethylenevinyl alcohol membrane (His-PEVA) is able to retain specific autoantibodies involved in antiphospholipid syndrome. To this end diluted patient pathogenic plasma containing high levels of anti-beta2-glycoprotein I (anti-beta2GPI) and antiprothrombin antibodies was processed through the functionalized cartridge. The adsorbed material was then eluted under mild conditions and analyzed; an enrichment of the eluted fractions in total IgG and more specifically in IgG2 subclass was observed, compared with the injected sample. Enzyme-linked immunosorbent assay tests showed a higher specific binding of antiprothrombin and anti-beta2GPI in these fractions. This was in accordance with the concomitant higher anticoagulant activity measured on the same fractions. All in vitro results clearly demonstrated the ability of the His-PEVA cartridge to preferentially adsorb these autoantibodies. Hence the functionalized cartridge represents a potential tool for the treatment of antiphospholipid syndrome by selective extracorporeal removal of IgG. 相似文献