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排序方式: 共有1710条查询结果,搜索用时 31 毫秒
931.
JF Baker-Malcolm L Haeffner-Gormley L Wang MW Anders C Thorpe 《Canadian Metallurgical Quarterly》1998,37(5):1383-1393
A range of 4-thiaacyl-CoA derivatives has been synthesized to study the bioactivation of cytotoxic fatty acids by the mitochondrial medium-chain acyl-CoA dehydrogenase and the peroxisomal acyl-CoA oxidase. Both enzymes catalyze alpha-proton abstraction from normal acyl-CoA substrates with elimination of a beta-hydride equivalent to the FAD prosthetic group. In competition with this oxidation reaction, 4-thiaacyl-CoA thioesters undergo dehydrogenase-catalyzed beta-elimination, providing that the corresponding thiolates are sufficiently good leaving groups and can be accommodated by the active site of the enzyme. Thus, the dehydrogenase catalyzes the elimination of 2-mercaptobenzothiazole and 4-nitrothiophenolate from 4-(2-benzothiazole)-4-thiabutanoyl-CoA and 4-(4-nitrophenyl)-4-thiabutanoyl-CoA, respectively. However, the 2,4-dinitrophenyl-analogue appears too bulky and the unsubstituted thiophenyl-derivative is insufficiently activated for significant elimination. Molecular modeling shows that steric interference from the flavin ring dictates a syn rather than an anti elimination. Acryloyl-CoA, the other product of 4-thiaacyl-CoA elimination reactions, is not a significant inactivator of the medium-chain dehydrogenase. In contrast, the irreversible inactivation observed during beta-elimination using 5,6-dichloro-4-thia-5-hexenoyl-CoA (DCTH-CoA), 5,6-dichloro-7,7,7-trifluoro-4-thia-5-heptenoyl-CoA (DCTFTH-CoA), and 6-chloro-5,5,6-trifluoro-4-thiahexanoyl-CoA (CTFTH-CoA) is caused by release of cytotoxic thiolate products within the active site of the dehydrogenase. The double bond between C5 and C6 found in the vinylic analogues DCTH- and DCTFTH-CoA is not essential for enzyme inactivation, although CTFTH-CoA is a weaker inhibitor of the dehydrogenase. Mechanism-based inactivation with CTFTH-CoA requires elimination, is unaffected by exogenous nucleophiles, and is strongly protected by octanoyl-CoA. The peroxisomal acyl-CoA oxidase efficiently oxidizes 4-thiaacyl-CoA analogues, but is only rapidly inactivated by DCTFTH-CoA. The variable ratio of elimination to oxidation observed for DCTH-, DCTFTH-, and CTFTH-CoA may influence the metabolism of the corresponding cytotoxic alkanoic acids in vivo. 相似文献
932.
A 66-year-old female underwent uneventful removal of parasagittal meningioma. At surgery, a piece of Biobond-soaked oxycellulose was applied to the lateral wall of the superior sagittal sinus for hemostasis. Her early postoperative course was complicated by focal but severe brain edema, which was adjacent to the hemostatic agent. Unlike foreign body granuloma previously reported, this complication was considered to be attributed to inflammatory reaction of Biobond, because of the early onset and fulminant edema despite of small volume of the mass lesion. Although there have been no previous reports of this complication, it should be kept in mind that intracranial application of Biobond may induce fulminant inflammatory reaction as seen in this patient. 相似文献
933.
AK Jain AJ DeFranzo MW Marks BW Loggie S Lentz 《Canadian Metallurgical Quarterly》1997,38(2):115-22; discussion 122-3
Exenterative pelvic surgery is commonly performed for advanced carcinoma of the cervix and selected cases of locally advanced colorectal cancers. Low-lying lesions that are locally invasive in contiguous organs require resection of the perineal body en bloc with the resected specimen. The resulting defect, both in the pelvis and the perineum, creates a difficult management problem. Dead space in the pelvis, especially with adjunctive irradiation, leads to delayed wound healing and prolapse of small bowel into the pelvis. Small bowel obstruction and/or fistula formation are the greatest sources of morbidity in the operative group. Fifteen patients underwent exenterative pelvic procedures (total exenteration, 1 patient; posterior exenteration, 8 patients; abdominoperineal resection, 6 patients). All patients were reconstructed by transpelvic placement of the rectus abdominis muscle (muscle only, 4 patients; muscle with skin grafting, 8 patients; musculocutaneous, 3 patients). Eighty-seven percent received radiation therapy. One patient had Crohn's disease and all others had carcinoma. Healing was complete in 12 of 15 patients at discharge. There were no complications related to pelvic dead space (i.e., bowel obstruction, perineal fistula), with a mean follow-up time of 24.3 months. Small bowel was effectively excluded from the pelvis to the level of the acetabular roof by computerized axial tomography scan. The transpelvic rectus abdominis muscle flap is effective in preventing major morbidity after exenterative pelvic surgery. 相似文献
934.
Frequency response analysis is applied to analyze NIR-TRS spectra in a tissue model with a simulated thrombus. The value changes in parameters obtained from frequency response analysis are correlated with heterogeneity position in three dimensions. The goal of this research is to noninvasively localize deep vein thrombosis in the human leg through the use of this novel combination. 相似文献
935.
A woman who presented with features of peripheral sensory, motor and autonomic neuropathy and amyloid deposits in the vitreous due to familial amyloid polyneuropathy (FAP) is described. Her father had died of a similar illness and one of her brothers and her two children had lesions suggestive of early amyloid deposits in the vitreous. Reports of familial amyloidosis are rare from Asian countries and it has not been reported in Sri Lanka previously. 相似文献
936.
937.
Photodynamic therapy (PDT) is a cancer treatment based on the interaction of light and a photosensitizing chemical. The photosensitizer protoporphyrin IX (PpIX) is generated via the haem biosynthetic pathway after administration of aminolaevulinic acid (ALA). The cellular microenvironment of tumours is hypoxic and acidotic relative to normal tissue, which may influence PpIX generation and compromise PDT efficacy. This study used bladder cancer cells, incubated with ALA at various oxygen tensions and H+ ion concentrations, and assessed the effects on PpIX generation and PDT sensitivity. PpIX production was reduced at 0%, 2.5% (19 mmHg) and 5% (38 mmHg) oxygen compared with that at 21% (160 mmHg) oxygen (0.15, 0.28 and 0.398 ng microg(-1) protein compared with 0.68 ng microg(-1) respectively; P < 0.05). The response to PDT was abolished by hypoxia, as a result of both reduced PpIX synthesis and reduced PDT toxicity. PpIX production was greater at pH 7.0 and 6.5 (0.75 and 0.66 ng microg(-1)) compared with that at pH 7.4 and 5.5 (0.41 and 0.55 ng microg(-1) respectively). PDT cytotoxicity was enhanced at lower pH values. These results suggest that ALA-induced PDT may be inhibited by hypoxia due to reduced intrinsic PpIX synthesis. Acidosis may slightly enhance the efficacy of ALA-induced PDT. 相似文献
938.
939.
940.
S Postovsky MW Ben Arush E Kassis R Elhasid N Krivoy 《Canadian Metallurgical Quarterly》1997,14(6):547-554
Fifty-two children suffering from different types of malignancies were included and evaluated for the pharmacokinetics of gentamicin thrice or single daily dosage protocols. All the study population received a total dose of 5 mg/kg daily. Thirty children received gentamicin thrice daily, and 22 were treated using the single daily protocol; all had fever and neutropenia when included. The individual pharmacokinetic parameters were calculated using a one-compartment model for two blood gentamicin samples. The mean (SD) t 1/2 (h), clearance (mL/min/BSA), Vss (L/kg), Cmax (micrograms/mL), and Cmin (micrograms/mL) were 3.05 (1.0) and 3.9 (0.6) h, 136 (61.3) and 99.9 (65.3) mL/min/BSA, 0.4035 (0.167) and 0.457 (0.17) L/kg, 5.2 (2.0) and 11.5 (4.2) micrograms/mL, 0.8 (0.6) and 0.18 (0.1) microgram/mL for thrice and single daily dosage schedules, respectively. The single gentamicin daily dose protocol had a significantly longer t 1/2, shorter clearance normalized to BSA, higher Cmax, and lower Cmin in comparison with the thrice daily schedule. We recommend the use of gentamicin at 5 mg/kg daily delivered as a single daily dose for pediatric cancer patients with fever and neutropenia, in spite of the measured pharmacokinetic differences, which in our opinion have no clinical significance. 相似文献