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991.
WA Gahl M Brantly MI Kaiser-Kupfer F Iwata S Hazelwood V Shotelersuk LF Duffy EM Kuehl J Troendle I Bernardini 《Canadian Metallurgical Quarterly》1998,338(18):1258-1264
BACKGROUND: Hermansky-Pudlak syndrome is characterized by oculocutaneous albinism, a storage-pool deficiency, and lysosomal accumulation of ceroid lipofuscin, which causes pulmonary fibrosis and granulomatous colitis in some cases. All identified affected patients in northwest Puerto Rico are homozygous for a 16-bp duplication in exon 15 of a recently cloned gene, HPS. We compared the clinical and laboratory characteristics of these patients with those of patients without the 16-bp duplication. METHODS: Forty-nine patients -- 27 Puerto Ricans and 22 patients from the mainland United States who were not of Puerto Rican descent -- were given a diagnosis on the basis of albinism and the absence of platelet dense bodies. We used the polymerase chain reaction to determine which patients carried the 16-bp duplication. RESULTS: Twenty-five of the Puerto Rican patients were homozygous for the 16-bp duplication, whereas none of the non-Puerto Rican patients carried this mutation. Like the patients without the duplication, the patients with the 16-bp duplication had a broad variation in pigmentation. Nine of 16 adults with the duplication, but none of the 10 without it, had a diffusing capacity for carbon monoxide that was less than 80 percent of the predicted value. High-resolution computed tomography in 12 patients with the 16-bp duplication revealed minimal fibrosis in 8, moderate fibrosis in 1, severe fibrosis in 1, and no fibrosis in 2. Computed tomography in eight patients without the duplication revealed minimal fibrosis in three and no fibrosis in the rest. Inflammatory bowel disease developed in eight patients (four in each group) between 3 and 25 years of age. CONCLUSIONS: The 16-bp duplication in exon 15 of HPS, which we found only in Puerto Rican patients, is associated with a broad range of pigmentation and an increased risk of restrictive lung disease in adults. 相似文献
992.
The object of the study was to compare two commercial root canal sealers: Ketac-Endo (a glass ionomer cement) and Fill Canal (a zinc oxide-eugenol cement). A total of 34 root canals from dog premolars with vital pulps were used. After instrumentation, the root canals were sealed with Ketac-Endo and Fill Canal cements using gutta-percha and a lateral condensation technique. After 270 days the animals were sacrificed with an anesthetic overdose and the maxillae and mandibles were removed and fixed in formalin for 48 h. After routine histological processing the sections were stained with hematoxylin-eosin and Mallory trichrome stains. Microscopic analysis revealed that Ketac-Endo cement presented better results than Fill Canal cement. 相似文献
993.
994.
WA Wells 《Canadian Metallurgical Quarterly》1998,5(8):R205-R206
995.
Classical microdialysis has some drawbacks. Two main issues in this respect are the time-consuming calculations (due to partial recovery of an analyte) and depletion near the sampling site. In this paper we describe a sampling method, called ultraslow microdialysis (usMD), and compare this with ultrafiltration (UF) at flow rates between 100 and 300 nL/min. As an example of an application of this method, we conducted a dual-enzyme analysis for simultaneous measurement of the glucose and lactate concentrations, demonstrating these sampling techniques in the subcutaneous tissue of the rat. For UF, the flow rates in vitro and in vivo were the same. For usMD, the recovery for glucose and lactate at the applied flow rates was 100%, in contrast to conventional microdialysis. Both sampling techniques have the potential of on-line in vivo monitoring, as well as the measurement of time profiles of analytes by continuous collection and off-line analysis afterward. 相似文献
996.
HS Willenberg SR Bornstein T Dumser M Ehrhart-Bornstein A Barocka GP Chrousos WA Scherbaum 《Canadian Metallurgical Quarterly》1998,24(3-4):963-967
Endocrine dysfunction may cause psychiatric symptoms and, vice versa, psychiatric diseases may lead to endocrine alterations. The adrenal as the end organ of both the hypothalamic-pituitary-adrenocortical and sympatho-adrenal axes is subject to the functional changes of the stress system. Thus, increased adrenal gland weight was observed previously in victims of violent suicide. This study was designed to analyze the morphological and morphodynamic changes of adrenals from suicide victims. We investigated 30 adrenals obtained from 15 suicide victims using immunohistochemistry and a computerized video system. In addition, apoptosis and cell proliferation were analyzed. We found a significant enlargement of the adrenal cortex to 158.8% (SD = 29.8%, p < 0.01) that was restricted to the two inner zones only (zona reticularis, 161.6 +/- 35.3%; zona fasciculata, 186.4 +/- 34.4%). This increase in adrenocortical size correlated with a decrease in the number of apoptotic cells within the zona fasciculata. In conclusion, these results clearly demonstrate chronic structural adrenal changes in suicide victims. The adrenal gland mirrors the functional changes of the stress system which leaves an imprint on the morphology of the gland. 相似文献
997.
EJ van Someren BF Vonk WA Thijssen JD Speelman PR Schuurman M Mirmiran DF Swaab 《Canadian Metallurgical Quarterly》1998,45(3):386-395
The human ether-a-go-go-related gene (HERG) encodes a K+ channel with biophysical properties nearly identical to the rapid component of the cardiac delayed rectifier K+ current (IKr). HERG/IKr channels are a prime target for the pharmacological management of arrhythmias and are selectively blocked by class III antiarrhythmic methanesulfonanilide drugs, such as dofetilide, E4031, and MK-499, at submicromolar concentrations. By contrast, the closely related bovine ether-a-go-go channel (BEAG) is 100-fold less sensitive to dofetilide. To identify the molecular determinants for dofetilide block, we first engineered chimeras between HERG and BEAG and then used site-directed mutagenesis to localize single amino acid residues responsible for block. Using constructs heterologously expressed in Xenopus oocytes, we found that transplantation of the S5-S6 linker from BEAG into HERG removed high-affinity block by dofetilide. A point mutation in the S5-S6 linker region, HERG S620T, abolished high-affinity block and interfered with C-type inactivation. Thus, our results indicate that important determinants of dofetilide binding are localized to the pore region of HERG. Since the loss of high-affinity drug binding was always correlated with a loss of C-type inactivation, it is possible that the changes observed in drug binding are due to indirect allosteric modifications in the structure of the channel protein and not to the direct interaction of dofetilide with the respective mutated site chains. However, the chimeric approach was not able to identify domains outside the S5-S6 linker region of the HERG channel as putative candidates involved in drug binding. Moreover, the reverse mutation BEAG T432S increased the affinity of BEAG K+ channels for dofetilide, whereas C-type inactivation could not be recovered. Thus, the serine in position HERG 620 may participate directly in dofetilide binding; however, an intact C-type inactivation process seems to be crucial for high-affinity drug binding. 相似文献
998.
Cruciferous vegetables, especially broccoli, may prevent cancer through anticarcinogenic compounds. For example, broccoli contains isothiocyanates that induce carcinogen-detoxifying enzymes. Glutathione transferase enzymes conjugate isothiocyanates, leading to excretion. We hypothesized that broccoli consumption in combination with the glutathione transferase M1 (GSTM1) null genotype would be associated with a lower prevalence of colorectal adenomas because of higher isothiocyanate levels. We used a case-control study of mainly asymptomatic subjects aged 50-74 years who underwent a screening sigmoidoscopy at either of two Southern California Kaiser Permanente Medical Centers during 1991-1993. Cases (n = 459) had a first-time diagnosis of histologically confirmed adenomas detected by flexible sigmoidoscopy. Controls (n = 507) had no polyp detected. Subjects had a 45-min in-person interview for information on various risk factors and basic demographic data and completed a 126-item, semiquantitative food frequency questionnaire. Blood samples were used for GSTM1 genotyping. Subjects with the highest quartile of broccoli intake (an average of 3.7 servings per week) had an odds ratio of 0.47 (95% confidence interval, 0.30-0.73) for colorectal adenomas, compared with subjects who reportedly never ate broccoli. When stratified by GSTM1 genotype, a protective effect of broccoli was observed only among subjects with the GSTM1 null genotype (P for trend, 0.001; P for interaction, 0.01). The observed broccoli-GSTM1 interaction is compatible with an isothiocyanate mechanism. 相似文献
999.
R Houlston S Bevan A Williams J Young M Dunlop P Rozen C Eng D Markie K Woodford-Richens MA Rodriguez-Bigas B Leggett K Neale R Phillips E Sheridan S Hodgson T Iwama D Eccles W Bodmer I Tomlinson 《Canadian Metallurgical Quarterly》1998,7(12):1907-1912
Juvenile polyps are present in a number of Mendelian disorders, sometimes in association only with gastrointestinal cancer [juvenile polyposis syndrome (JPS)] and sometimes as part of known syndromes (Cowden, Gorlin and Banayan-Zonana) in association with developmental abnormalities, dysmorphic features or extra-intestinal tumours. Recently, a gene for JPS was mapped to 18q21.1 and the candidate gene DPC4 (SMAD4) was shown to carry frameshift mutations in some JPS families. We have analysed eight JPS families for linkage to DPC4. Overall, there was no evidence for linkage to DPC4; linkage could be excluded in two of the eight pedigrees and was unlikely in two others. We then tested these eight families and a further 13 familial and sporadic JPS cases for germline mutations in DPC4. Just one germline DPC4 mutation was found (in a familial JPS patient from a pedigree unsuitable for linkage analysis). Like all three previously reported germline mutations, this variant occurred towards the C-terminus of the DPC4 protein. However, our patient's mutation is a missense change (R361C); somatic missense mutations in DPC4 have been reported previously in tumours. We therefore confirm DPC4 as a cause of JPS, but show that there is considerable remaining, uncharacterized genetic heterogeneity in this disease. 相似文献
1000.
M Kruse SR Bornstein K Uhlmann G Paeth WA Scherbaum 《Canadian Metallurgical Quarterly》1998,24(3-4):587-590
OB protein leptin inhibits the secretion of cortisol in primary cultures of bovine adrenocortical cells and down-regulates 17alpha-hydroxylase cytochrome P450 mRNA expression. To analyze if leptin regulates other major enzymes involved in adrenal steroidogenesis we tested its effect on mRNA expression for two further key enzymes, C21-hydroxylase (P450C21) and side-chain cleavage enzyme (P450SCC). Cultured bovine cortical cells were stimulated for 24 hours with 10 nM ACTH, with 10 nM ACTH plus 100 ng/ml leptin or left unstimulated as controls. Stimulation with ACTH led to a 1.75-fold increase of P450C21 mRNA and a 3.31-fold increase of P450SCC mRNA compared to unstimulated controls. Addition of leptin led to a reduction of ACTH-stimulated mRNA accumulation of 73% for P450C21 and of 45% for P450SCC. We therefore suggest that leptin reduces cortisol synthesis in the adrenal by down-regulating the steroid producing enzyme cascade in the cortical cell. 相似文献