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11.
A 74-year-old patient sought treatment for visual obscuration and clinically had signs of Graves orbitopathy. Past medical history was unremarkable except for the use of antihypertensive medication. During the hospital admission, a fluorescent treponemal antibody absorption test was reactive, indicating infection with syphilis at some time in the past. Visual deterioration despite oral corticosteroid therapy prompted orbital decompression. At the time of surgery, she sustained a globe rupture. Presumably, syphilitic scleritis was responsible, in part, for scleral thinning and weakening, predisposing her to this complication. To the authors' knowledge, globe rupture has not been previously reported during orbital decompression. 相似文献
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B Grassi LB Gladden CM Stary PD Wagner MC Hogan 《Canadian Metallurgical Quarterly》1998,85(4):1404-1412
To test the hypothesis that muscle O2 uptake (V(O2)) on-kinetics is limited, at least in part, by peripheral O2 diffusion, we determined the V(O2) on-kinetics in 1) normoxia (Control); 2) hyperoxic gas breathing (Hyperoxia); and 3) hyperoxia and the administration of a drug (RSR-13, Allos Therapeutics), which right-shifts the Hb-O2 dissociation curve (Hyperoxia+RSR-13). The study was conducted in isolated canine gastrocnemius muscles (n = 5) during transitions from rest to 3 min of electrically stimulated isometric tetanic contractions (200-ms trains, 50 Hz; 1 contraction/2 s; 60-70% peak V(O2)). In all conditions, before and during contractions, muscle was pump perfused with constantly elevated blood flow (Q), at a level measured at steady state during contractions in preliminary trials with spontaneous Q x Adenosine was infused intra-arterially to prevent inordinate pressure increases with the elevated Q x Q was measured continuously, arterial and popliteal venous O2 concentrations were determined at rest and at 5- to 7-s intervals during contractions, and V(O2) was calculated as Q x arteriovenous O2 content difference. PO2 at 50% HbO2 saturation (P50) was calculated. Mean capillary PO2 (Pc(O2)) was estimated by numerical integration. P50 was higher in Hyperoxia+RSR-13 [40 +/- 1 (SE) Torr] than in Control and in Hyperoxia (31 +/- 1 Torr). After 15 s of contractions, Pc(O2) was higher in Hyperoxia (97 +/- 9 Torr) vs. Control (53 +/- 3 Torr) and in Hyperoxia+RSR-13 (197 +/- 39 Torr) vs. Hyperoxia. The time to reach 63% of the difference between baseline and steady-state V(O2) during contractions was 24.7 +/- 2.7 s in Control, 26.3 +/- 0.8 s in Hyperoxia, and 24.7 +/- 1.1 s in Hyperoxia+RSR-13 (not significant). Enhancement of peripheral O2 diffusion (obtained by increased PcO2 at constant O2 delivery) during the rest-to-contraction (60-70% of peak V(O2)) transition did not affect muscle V(O2) on- kinetics. 相似文献
14.
MB Hossain D van der Helm FJ Schmitz EO Pordesimo RA Magarian KL Meyer LB Overacre BW Day 《Canadian Metallurgical Quarterly》1994,37(11):1670-1683
Molecular structures and conformational characteristics of a series of 1,1-dichloro-2,2,3-triarylcyclopropanes (DTACs), which were reported previously to be distinctly antiestrogenic and inhibitors of the estrogen-receptor-positive MCF-7 human breast cancer cells in culture, are reported. In addition, structural and conformational features of the DTACs were compared to the first-known nonsteroidal antiestrogen, MER25, and the clinically useful antiestrogen Tamoxifen. The molecular structures of four DTAC compounds were determined by X-ray diffraction. Crystallographic structures show that the DTAC molecules have nearly the same relative conformation for the three aryl rings which is designated as a "nonpropeller" conformation in contrast to the observed "propeller" conformation for the three rings in all known triarylethylenes. Systematic conformational searches were performed to find the conformational preferences of DTACs, MER25, and Tamoxifen using idealized model compounds built from their respective crystal structure. Energy-minimization and conformational-search studies demonstrated that all DTAC molecules have a common, single global minimum energy conformer for their central core containing the dichlorotriarylcyclopropyl system, which is similar to that found in their crystal structures. Conformational search of MER25 showed that the molecule can assume a number of low-energy conformers of which two, one anti (A1) and one gauche (G1A), have about the same energy. The anti conformation is similar to the one observed in its crystal structure and resembles the estrogenic E-isomer of Tamoxifen, while the lowest energy gauche conformer of MER25 resembles more closely the antiestrogenic Z-isomer of Tamoxifen. NMR spectroscopic analysis of MER25 showed that the molecule exists predominantly in the anti conformation in solution. A comparative review of the structural features and bioactivities of Tamoxifen, DTACs, and MER25 provides a possible explanation for their low estrogen receptor binding affinity which is common to these compounds together with their antiestrogenic activity. 相似文献
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Primary cultures of neonatal rat aortic smooth muscle cells inoculated at high densities (1 X 10(6) cells/25 cm2 Falcon flask) with adequate nutrient media and pH control grow rapidly and form multilayers of cells with typical "hill and valley" organization. After 10 days growth insoluble elastin formation could be visualized by phase contrast microscopy as small particles which grew rapidly to become larger irregular refractile aggregates and later coalesced to form larger aggregates and small fibres. With light and electronmicroscopy, elastin was the predominant matrix protein formed, with the "hill regions" of cultures containing abundant elastin aggregates and some collagen. In 2-week-old cultures differentiation could be observed within the cell multilayer. The older deeper cells contained more protein synthesis organelles and myofilaments and were in close association with large often coalescing elastin aggregates; compared to younger more superficial cells which contained more free polyribosomes less myofilaments, and were associated with fewer and small elastin aggregates. In older cultures this differentiation was not apparent; the cells contained many myofilaments, dense bodies, and lysosomes. Elastin aggregates and newly formed elastic fibres were abundant in the matrix. Quantitative analysis of insoluble elastin formation in the cell layer during the 4-week culture period indicated continuous biosynthesis and deposition which paralleled that of desmosine formation. Amino-acid analysis of a hot alkali insoluble residue (regarded as elastin) from 30-day-old cultures gave a profile identical with neonatal rat aortic elastin in vivo. Insoluble collagen formation in the cell layer tended to plateau after the log phase of growth was completed (10 days). Proteoglycans were found predominantly in the supernatant media. Glycosaminoglycan analysis revealed a profile of dermatan sulphate (32%), chondroitin 4-sulphate (43%), keratan and heparan sulphate (30%), with only a trace of hyaluronic acid. This study indicates that primary cultures of neonatal rat aortic smooth muscle cells remain differentiated in culture and have the unique capacity to continue to synthesize and deposit large amounts (mg) of insoluble elastin which aggregate and from elastic fibres in vitro. 相似文献
17.
IE van der Horst-Bruinsma JM Hazes GM Schreuder TR Radstake P Barrera LB van de Putte D Mustamu D van Schaardenburg FC Breedveld RR de Vries 《Canadian Metallurgical Quarterly》1998,57(11):672-675
OBJECTIVE: It has recently been observed that non-inherited maternal DR4 antigens (NIMAs) of DR4 negative rheumatoid arthritis (RA) patients were increased compared with non-inherited paternal DR4 antigens (NIPAs). The aim of this study was to determine the prevalence of non-inherited DR4 antigens and DRB1 alleles in parents of RA patients. METHODS: HLA-DR serology and DRB1 typing was performed in 97 RA patients and their parents. NIMA and NIPA frequencies were compared, stratified according to the presence of DR4 and/or the shared epitope (SE). RESULTS: In DR4 negative patients, NIMA DR4 was increased compared with NIPA DR4 (OR 3.10, 95% CI 0.76, 12.70). When combined with results from a previous study this increase was significant (OR 3.65, 95% CI 1.29, 10.31). The NIMA effect of SE positive DR4 subtypes in this study (OR 4.73, 95% CI 0.94, 23.8) was stronger than the NIMA effect of combined SE positive DRB1 alleles (OR 2.19 95% CI 0.36, 13.22). CONCLUSIONS: The association between non-inherited maternal HLA-DR4 alleles and the susceptibility to RA was observed in two independent populations. 相似文献
18.
AIM: To develop an acute tolerant model in describing relationship between diltiazem (Dil) concentrations in plasma and PR intervals on ECG in men. METHOD: Both plasma concentrations of Dil and changes of ECG were simultaneously determined after po Dil 90 mg in 8 men. RESULTS: A two-compartmental pharmacokinetic model with first-order input gave a good fitting for the plasma concentration of Dil. Corresponding pharmacokinetic parameters were estimated: t1/2 beta, 5.9 +/- 1.0 h; MRT, 15.9 +/- 1.0 h; t0, 0.38 +/- 0.07 h; tmax, 2.7 +/- 0.4 h, and Cmax, 161 +/- 60 micrograms.L-1. The good fittings for plasma concentration-effect data were obtained with tolerant model E = S x C/(1 + T/T50). The pharmacodynamic parameters were given as follows: S, 829 +/- 293 s.g-1.L; Kt0, 0.037 +/- 0.024 h-1 and T50, 10 +/- 4 micrograms.L-1. CONCLUSION: Relationship between Dil concentrations in plasma and PR interval changes in men after po 90 mg was described using an acute tolerant model. 相似文献
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SH Kaufmann D Peereboom CA Buckwalter PA Svingen LB Grochow RC Donehower EK Rowinsky 《Canadian Metallurgical Quarterly》1996,88(11):734-741
BACKGROUND: Topotecan (TPT) is a topoisomerase I poison that exhibits antineoplastic activity. Analysis of the cytotoxic effects of combinations of TPT and other anticancer agents has been limited. PURPOSE: We assessed the cytotoxic effects produced by combinations of TPT and other antineoplastic agents in experiments involving multiple human cancer cell lines of diverse histologic origins. METHODS: The cytotoxic effects of various antimetabolites (fluorouracil, methotrexate, or cytarabine), antimicrotubule agents (vincristine or paclitaxel [Taxol]), DNA alkylating agents (melphalan, bis[chloroethyl]nitrosourea [BCNU], or 4-hydroperoxycyclophosphamide [4HC]), and a DNA-platinating agent (cisplatin), alone and in combination with TPT, were measured in clonogenic (i.e., colony-forming) assays. HCT8 ileocecal adenocarcinoma, A549 non-small-cell lung carcinoma, NCI-H82ras(H) lung cancer, T98G glioblastoma, and MCF-7 breast cancer cell lines were used in these assays. The data were analyzed by the median effect method, primarily under the assumption that drug mechanisms of action were mutually nonexclusive (i.e., completely independent of one another). For each level of cytotoxicity (ranging from 5% to 95%), a drug combination index (CI) was calculated. A CI less than 1 indicated synergy (i.e., the effect of the combination was greater than that expected from the additive effects of the component agents), a CI equal to 1 indicated additivity, and a CI greater than 1 indicated antagonism (the effect of the combination was less than that expected from the additive effects of the component agents). RESULTS: When the mechanisms of drug action were assumed to be mutually nonexclusive, virtually all CIs for combinations of TPT and either antimetabolites or antimicrotubule agents revealed cytotoxic effects that were less than additive. The CIs calculated at low-to-intermediate levels of cytotoxicity for combinations of TPT and the DNA alkylating agents melphalan, BCNU, and 4HC also showed drug effects that were less than additive; in most cases, however, nearly additive or even synergistic effects were observed with these same drug combinations at high levels of cytotoxicity (i.e., at > or = 90% inhibition of colony formation). Results obtained with combinations of TPT and cisplatin varied according to the cell line examined. With A549 cells, less than additive effects were seen at low-to-intermediate levels of cytotoxicity, and more than additive effects were seen at high levels of cytotoxicity. With NCI-H82ras(H) cells, synergy was observed over most of the cytotoxicity range. CONCLUSIONS AND IMPLICATIONS: TPT cytotoxicity appears to be enhanced more by combination with certain DNA-damaging agents than by combination with antimetabolites or antimicrotubule agents. Interactions between TPT and other drugs can vary depending on the cell type examined. Further investigation is required to determine the basis of the observed effects and to determine whether these in vitro findings are predictive of results obtained in vivo. 相似文献