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81.
Discovery of selective, small-molecule inhibitors of RNA complexes--I. The Tat protein/TAR RNA complexes required for HIV-1 transcription 总被引:2,自引:0,他引:2
HY Mei DP Mack AA Galan NS Halim A Heldsinger JA Loo DW Moreland KA Sannes-Lowery L Sharmeen HN Truong AW Czarnik 《Canadian Metallurgical Quarterly》1997,5(6):1173-1184
We have developed a therapeutic program focusing on the inhibition of a human immunodeficiency virus-1 specific protein-RNA interaction. This program begins with a search for small organic molecules that would interfere with the binding of Tat protein to TAR RNA. The methodologies chosen to study the HIV-1 Tat-TAR interaction and inhibition include gel mobility shift assays, scintillation proximity assays, filtration assays, and mass spectrometry. These methods helped establish in vitro high-throughput screening assays which rapidly identified Tat-TAR inhibitors from our corporate compound library. Tat-activated reporter gene assays were then used to investigate the cellular activities of the Tat-TAR inhibitors. The cellular activity, selectivity, and toxicity data for select Tat-TAR inhibitors were determined. Evaluation of both the cellular data and the Tat-TAR inhibition results led to further testing in anti-HIV-1 infection assays. 相似文献
82.
AV Pugaev NS Bogomolova VV Bagdasarov KB Sirozhitdinov LN Vinogradova 《Canadian Metallurgical Quarterly》1997,(3):123-125
Pharmacokinetics was studied of kefsole administered by intravenous and endolymphatic routes to patients (n = 23) with acute pancreatitis. The studies made showed that intravenous route for the drug administration makes for a quicker entering of the antibiotic into the peritoneal exudate. Apart from these reasons, endolymphatic antibacterial therapy does not appear to avert the development of complications involving pus-formation/discharging in acute pancreatitis and does not seem to be essential in the complex of therapeutic measures to be applied for treating the above patients. 相似文献
83.
NS Ponomareva OG Voskresenskaia AA Kamenski? VP Golubovich IP Ashmarin 《Canadian Metallurgical Quarterly》1998,48(3):471-477
Ethinylestradiol (EE) has evident paradoxical effects on cancer risk for human breast and hepatic cancer which parallel in some respects its effects on estrogen-induced neoplasms in the hamster kidney and liver. EE has been shown to be only weakly carcinogenic in the hamster kidney, but the most potent carcinogenic estrogen in the hamster liver following prolonged treatment. Unexpectedly, when EE and potent carcinogenic estrogens, such as diethylstilbestrol (DES), 17beta-estradiol (E2) and Moxestrol (MOX), are administered concomitantly, estrogen-induced carcinogenesis in the kidney is completely prevented. In studying this novel finding, we found that, compared with E2 exposure alone, EE at 0.05 and 1.0 nM significantly (P < 0.001) inhibited the rise in proliferation of cultured primary hamster proximal renal tubular (PRT) cells in the presence of E2 (1.0 nM). Consistent with these findings, combined EE + DES treatment for 5.0 months reduced hamster kidney c-myc, c-fos and c-jun RNA expression to 43, 37 and 52%, respectively, compared with levels observed after DES treatment alone. Interestingly, TAM + DES treatment for the same period also resulted in the same low level of RNA expression of these proto-oncogenes. c-MYC, c-FOS and c-JUN protein products were comparably reduced after either EE + DES or TAM + DES treatment. It appears that c-fos expression and c-FOS protein levels in the hamster kidney were more responsive to TAM inhibition. These data demonstrate that EE possesses unique anti-tumorigenic properties in vivo in the hamster kidney. Additionally, the observed anti-estrogen-like effect of EE on cell proliferation of cultured PRT cells suggests that EE may interfere critically with estrogen receptor (ER)-mediated mitogenic pathway(s) affected by potent carcinogenic estrogens, thus preventing subsequent gene dysregulation and, hence, tumor development. Based on competition studies, the differential binding of EE to hamster kidney ER relative to that of the other estrogens (E2, DES, MOX) appears not to contribute to the prevention of estrogen carcinogenesis at this organ site by EE. 相似文献
84.
The endogenous protease(s) activated crystal toxin from Bacillus thuringiensis subsp. kurstaki was purified and examined. The purified toxin was homogenous, as demonstrated by two-dimensional polyacrylamide gel electrophoresis and contained 1.38 mumoles neutral sugar and 9 nmoles sialic acid per mg protein amino terminal amino acid sequence data revealed that the toxin is a cleavage product of 132 kDa protoxin with glutamic acid-30 of the deduced amino acid sequence of the crystal protein (Schnepf, H.E., Wong, H.C. and Whiteley, H.R. (1985) J. Biol. Chem. 260: 6264-6272) at the amino terminus. 相似文献
85.
86.
An alkylation method of docetaxel at the C-10 position has been established by a radical coupling reaction using a 10-xanthate derivative of 7-O-TES-10-deacetylbaccatin III and appropriate alkenes. In addition the cytotoxic activity of 10-alkylated docetaxel analogs was evaluated. Among these analogs, a derivative having a methoxycarbonyl group at the end of the alkyl moiety exhibited more potent cytotoxic activity than docetaxel. 相似文献
87.
88.
During recent years, ceramide has received a lot of attention as a possible mediator of the cellular responses to a variety of apoptotic stimuli. In a manner analogous to generation of its sibling diacylglycerol, ceramide is generated by a phospholipase-C-type reaction from its lipid precursor sphingomyelin. Two observations led to the proposal that ceramide plays a role in apoptosis: (1) treatment of cells with tumor necrosis factor or other inducers of apoptosis leads to activation of sphingomyelinases and to an increase in cellular ceramide levels; (2) ectopic generation or administration of ceramide can mimic apoptotic cell death. Recently, several observations have challenged the notion that ceramide is an important cell-death mediator and have prompted a re-evaluation of previously published results. 相似文献
89.
90.
NS Silverman MW Sullivan DL Jungkind V Weinblatt K Beavis RJ Wapner 《Canadian Metallurgical Quarterly》1994,84(6):1021-1024
OBJECTIVE: To assess the frequency of transient bacteremia among women undergoing transabdominal and transcervical chorionic villus sampling (CVS). METHODS: One hundred fourteen women undergoing CVS consented to participate in a university review board-approved study protocol. Exclusion criteria included known cardiac valve anomaly or replacement (or other prosthetic) and antibiotic use within the preceding 21 days. Blood cultures (aerobic and anaerobic) were drawn by a single operator on all patients, before CVS and within 15 minutes after completing CVS. Either the catheter tip or needle tip aspirate from each procedure was also sent for culture. RESULTS: Post-procedure bacteremia was detected in two (1.8%) of the patients undergoing CVS. These two patients both had their procedures performed transcervically, resulting in a 4.1% (two of 49) bacteremia rate after transcervical CVS, compared to none (zero of 65) in the transabdominal group (P = .36). The incidence of positive cultures from sampling instruments was also higher in the transcervical group (16.3 versus 0%; P = .003), but did not result in comparable rates of bacteremia among patients with positive instrument cultures. CONCLUSIONS: In this study, CVS was associated with a low rate of bacteremia, regardless of the procedure route. Recommendations for antibiotic prophylaxis in women with abnormal cardiac valves should parallel those for spontaneous vaginal delivery and other comparable genitourinary procedures. 相似文献