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排序方式: 共有310条查询结果,搜索用时 15 毫秒
31.
Brabec V Christofis P Slámová M Kostrhunová H Nováková O Najajreh Y Gibson D Kaspárková J 《Biochemical pharmacology》2007,73(12):1887-1900
A new tetrafunctional dinuclear platinum complex trans,trans-[{PtCl2(NH3)}2(piperazine)] with sterically rigid linking group was designed, synthesized and characterized. In this novel molecule, the DNA-binding features of two classes of the platinum compounds with proven antitumor activity are combined, namely trans oriented bifunctional mononuclear platinum complexes with a heterocyclic ligand and polynuclear platinum complexes. DNA-binding mode of this new complex was analyzed by various methods of molecular biology and biophysics. The complex coordinates DNA in a unique way and interstrand and intrastrand cross-links are the predominant lesions formed in DNA in cell-free media and in absence of proteins. An intriguing aspect of trans,trans-[{PtCl2(NH3)}2(piperazine)] is that, using a semi-rigid linker, interstrand cross-linking is diminished relative to other dinuclear platinum complexes with flexible linking groups and lesions that span several base pairs, such as tri- and tetrafunctional adducts, become unlikely. In addition, in contrast to the inability of trans,trans-[{PtCl2(NH3)}2(piperazine)] to cross-link two DNA duplexes, the results of the present work convincingly demonstrate that this dinuclear platinum complex forms specific DNA lesions which can efficiently cross-link proteins to DNA. The results substantiate the view that trans,trans-[{PtCl2(NH3)}2(piperazine)] or its analogues could be used as a tool for studies of DNA properties and their interactions or as a potential antitumor agent. The latter view is also corroborated by the observation that trans,trans-[{PtCl2(NH3)}2(piperazine)] is a more effective cytotoxic agent than cisplatin against human tumor ovarian cell lines. 相似文献
32.
Abstract: A range of Nα‐Fmoc‐protected amino acids, including those that contain t‐butyl moiety, have been synthesized by employing Fmoc‐Cl utilizing the activated, commercial zinc dust‐promoted synthesis of carbamates under neutral conditions.A general procedure is described that circumvents the oligomerization side reaction normally noticed in Schotten–Baumann conditions. It is a simple, convenient and clean method. Thus, Fmoc‐amino acids are obtained in high yield (85–92%) and purity as checked by thin‐layer chromatography, high‐performance liquid chromatography and other physical methods. 相似文献
33.
34.
《Human immunology》2015,76(9):657-662
The tyrosine kinase Fyn phosphorylates tyrosine residues on key targets involved in early T-cell signal transduction. T-cell signal transduction is one essential step for acute transplant rejection. The aim of this study was to evaluate the association of Fyn −93A>G single nucleotide polymorphism (SNP) (rs706895) with the susceptibility to acute rejection episodes in liver transplantation. In total, 72 liver transplant recipients with one biopsy proven acute rejection (S-BPAR), 56 with multiple BPAR (M-BPAR), 105 without BPAR (No-BPAR), and 145 healthy controls were enrolled in this case-control study. The SNP was genotyped by polymerase chain reaction–allele specific restriction enzyme analysis (PCR–ASRA) and was analyzed for a recessive and a dominant model. The Fyn −93G allele exhibits in healthy controls a statistically significant lower frequency than in liver recipients (18% vs. 24%; p = 0.046) or in liver recipients with BPAR (18% vs. 27%; p = 0.017). However, the genotype and allele frequencies of the Fyn −93A>G SNP demonstrate no significant differences between recipients with acute rejection episodes (S-BPAR and M-BPAR) and No-BPAR recipients. Thus our results provide no evidence that the Fyn −93A>G SNP contributes to the susceptibility to acute liver transplant rejection in a Caucasian population. 相似文献
35.
Engle JW Severin GW Barnhart TE Knutson LD Nickles RJ 《Applied radiation and isotopes》2012,70(2):355-359
We have measured the cross section for production of the medically interesting isotope 34mCl, along with 38Cl and 41Ar, using deuteron bombardments of 36Ar and 40Ar below 8.4 MeV. ALICE/ASH analytical codes were employed to determine the shape of nuclear excitation functions, and experiments were performed using the University of Wisconsin tandem electrostatic accelerator to irradiate thin targets of argon gas. 相似文献
36.
S. H. Liu J. L. Lai R. H. Lin M. J. Lin S. Y. Lin-Shiau 《Naunyn-Schmiedeberg's archives of pharmacology》1997,356(4):500-504
The contractile and electrical properties of the mouse diaphragm during endotoxemia were studied, and the possible role of
nitric oxide (NO) on these changes was investigated. The mice were injected intraperitoneally with E. coli. lipopolysaccharide
(endotoxin, LPS) at various times before isolation of the diaphragm to induce endotoxemia. It was observed that direct twitch
tension was slightly increased, and that there was a significant increase in tetanic tension when compared with controls.
The potentiation of direct twitch tension induced by a Cl–-channel blocker (9-anthracene carboxylic acid), but not the potentiation by a Na+-channel activator (veratridine) or by K+-channel blockers (uranyl ion, 4-aminopyridine and tetraethylammonium ion), was attenuated in the diaphragm of LPS-treated
mice. Moreover, the resting membrane potential was significantly reduced and the membrane input resistance was significantly
increased, largely due to a decrease in Cl–-conductance. However, the membrane K+-conductance remained unaltered. These results imply that the sarcolemmal Cl–-channel is markedly affected in the mouse diaphragm during endotoxemia. These changes of contractile and electrical characteristics
of the mouse diaphragm during endotoxemia could be reversed by treatment with dexamethasone and NG-nitro-l-arginine (NO synthase inhibitors). On the other hand, in in vitro studies, LPS (20 μg/ml), by itself, applied directly to
the diaphragm, did not alter the muscle contractions or the membrane potentials. A NO donor, added to the diaphragm bath,
increased the tetanus/twitch ratio and induced a transient depolarization. All of these findings suggest that LPS may, at
least in part, affect the sarcolemmal electrical properties and muscle contractions during endotoxemia through the l-arginine:NO pathway.
Received: 3 February 1997 / Accepted: 16 May 1997 相似文献
37.
BACKGROUND: IL-9 and IL-13 induce airway goblet cell metaplasia, which is associated with expression of a Ca(2+)-activated Cl channel, hCLCA1. OBJECTIVE: As UTP stimulates both mucin secretion and Cl ion transport via a Ca(2+)-dependent pathway, the purpose of this study is to determine whether IL-9 and IL-13 affect UTP-induced Cl ion transport in human bronchial epithelial cell line 16HBE cells, and if they do, to elucidate whether such an effect is associated with hCLCA1 expression. METHODS: The increases in short-circuit current (I(sc)) in response to UTP were measured in the presence of amiloride by the Ussing chamber method. The morphology of epithelial cells was assessed by light microscopic findings, and hCLCA1 expression was investigated by immunocytochemistry and immunoblotting. RESULTS: UTP-induced increases in I(sc) in the cells treated with IL-9 or IL-13 for 48 h were greater than those in non-treated cells, and the potency of IL-13 was greater than that of IL-9. Pre-treatment with Ca(2+)-activated Cl channel inhibitors diisothocyanatostilbene-2, 2-disulphonic acid and niflumic acid completely inhibited the augmenting effects of IL-9 and IL-13 on I(sc). The epithelial layer of the cells treated with IL-9 or IL-13 was thicker than that of non-treated cells. The expression of hCLCA1 protein was induced by IL-13 in a concentration-dependent manner. These effects of IL-13 were more potent than those of IL-9. CONCLUSION: IL-9 and IL-13 augmented UTP-induced Cl ion transport, probably via proliferation of the cells with hCLCA1 expression, and IL-13 was more potent than IL-9 in producing such an effect in 16HBE cells. 相似文献
38.
Evidence was obtained for catecholamine-stimulated adenylate cyclase activity in particulate fractions of frog and rabbit corneal epithelium. Epinephrine (10(-5)M) stimulated adenylate cyclase by 22 and 53% in the frog and rabbit, respectively. The corresponding changes were statistically significant (P less than 0.01) when the data was analyzed using paired variates. Preincubation with 10(-4)M propranolol eliminated any stimulatory effect by 10(-5)M isoproterenol. Adenylate cyclase activity derived from either source was activated several fold by either 10 mM NaF or 10(-5)MGpp (NH)p. Soluble fractions of homogenized frog corneal epithelium contained cyclic AMP-dependent protein kinase activity which was half-maximally stimulated by about 6 nM cyclic AMP. Evidence was also obtained for the presence of protein substrates of cyclic AMP dependent protein kinase in frog corneal epithelium. With exogenous cyclic AMP and protein kinase, a rapid 32P labelling of proteins having approximate molecular weights of 56, 46, 23 and 21 K was obtained with sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis. A less marked and slower increase in phosphoprotein formation was observed when corneal membranes were incubated with cyclic AMP in the absence of added protein kinase. 相似文献
39.
1. The β-receptor stimulant effects of Sm220Cl, dl-N- (1,1-dimethyl-3-phenylpropyl)-2-hydroxy-2(3,4-dihydroxy-2-methoxyphenyl)ethylamine, and (-)-isoprenaline have been compared in isolated atrial (β1) and tracheal (β2) preparations from guinea-pigs and cats. 2. The compounds were also tested for their ability to increase the heart rate (β1), reduce serotonin-induced increases in pulmonary resistance (β2), and decrease soleus muscle contractility (β2) in vivo in the two species. 3. In all experiments cumulative concentration or dose-effect curves were established, EC50 or ED50 values obtained and molar activity-ratios (Sm220Cl: (-)-isoprenaline) calculated. 4. Calculated selectivity ratios [activity-ratio (heart):activity-ratio (bronchial smooth muscle)] from the in vitro experiments showed that Sm220Cl possessed β2-receptor selectivity. This was more marked in guinea-pig than in cat preparations. 5. In the anaesthetized animals this species difference was more apparent; in cats Sm220Cl was non-selective in its actions for β1- and β2-receptor mediated responses, while marked β2-receptor selectivity was obtained in the guinea-pig. 6. Since in both species the activity-ratios for β2-receptor mediated actions are similar, the differences in the β1/β2-receptor selectivity of Sm220Cl are caused by the divergent cardiac effects produced by the drug. 相似文献
40.
The unidirectional fluxes of Na+ and Cl? across the isolated toad ciliary epithelium were measured under short-circuit conditions. In a normal medium, the transepithelial potential difference was about 4 mV, the epithelial side being negative with respect to the stroma side. The short-circuit current (SCC) was 46 μA/cm2 and the average electrical conductance was 11 mmhos/cm2. Both the Na+ and Cl? fluxes from the stromal to epithelial side were greater than those in the opposite direction and the net Cl? flux was 4 to 5 times greater than the net Na+ flux. In the stromal tirection, both the Na+ and Cl? fluxes were linearly related to the SCC, and the sum of the partial ionic conductances of Na+ and Cl? exceeded the electrical conductance. No correlation between the SCC and the Cl? or Na+ flux was found in the opposite direction and the sum of the partial ionic conductance agreed well with the electrical conductance. In the presence of either theophylline in 10 mm or ouabain in 1 mm, the SCC was decreased by about 70% and unidirectional fluxes of either direction were increased in accordance with the increase in the electrical conductance, except for the stromal to epithelial Cl? and Na+ fluxes in the presence of theophylline and ouabain, respectively. The data indicate that electrogenic Cl? transport is the major function and the major source of the SCC in the epithelium. 相似文献