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121.
P McLaughlin AJ Grillo-López BK Link R Levy MS Czuczman ME Williams MR Heyman I Bence-Bruckler CA White F Cabanillas V Jain AD Ho J Lister K Wey D Shen BK Dallaire 《Canadian Metallurgical Quarterly》1998,16(8):2825-2833
PURPOSE: The CD20 antigen is expressed on more than 90% of B-cell lymphomas. It is appealing for targeted therapy, because it does not shed or modulate. A chimeric monoclonal antibody more effectively mediates host effector functions and is itself less immunogenic than are murine antibodies. PATIENTS AND METHODS: This was a multiinstitutional trial of the chimeric anti-CD20 antibody, IDEC-C2B8. Patients with relapsed low grade or follicular lymphoma received an outpatient treatment course of IDEC-C2B8 375 mg/m2 intravenously weekly for four doses. RESULTS: From 31 centers, 166 patients were entered. Of this intent-to-treat group, 48% responded. With a median follow-up duration of 11.8 months, the projected median time to progression for responders is 13.0 months. Serum antibody levels were sustained longer after the fourth infusion than after the first, and were higher in responders and in patients with lower tumor burden. The majority of adverse events occurred during the first infusion and were grade 1 or 2; fever and chills were the most common events. Only 12% of patients had grade 3 and 3% grade 4 toxicities. A human antichimeric antibody was detected in only one patient. CONCLUSION: The response rate of 48% with IDEC-C2B8 is comparable to results with single-agent cytotoxic chemotherapy. Toxicity was mild. Attention needs to be paid to the rate of antibody infusion, with titration according to toxicity. Further investigation of this agent is warranted, including its use in conjunction with standard chemotherapy. 相似文献
122.
DJ Kempf RA Rode Y Xu E Sun ME Heath-Chiozzi J Valdes AJ Japour S Danner C Boucher A Molla JM Leonard 《Canadian Metallurgical Quarterly》1998,12(5):F9-14
OBJECTIVE: To determine markers that are associated with the durability of virologic response to therapy with HIV protease inhibitors in HIV-infected individuals. DESIGN: This study encompassed two retrospective analyses of the duration of virologic response to protease inhibitor therapy. The first analysis included 29 patients receiving either monotherapy or combination therapy with the protease inhibitor ritonavir whose plasma HIV RNA levels rebounded from the point of greatest decline with mutations associated with resistance to ritonavir. The second analysis included a cohort of 102 patients who initially responded to randomized treatment with either monotherapy with ritonavir or combination therapy with ritonavir and zidovudine. METHODS: Durability of response was defined as the time from the initiation of therapy to the point at which plasma HIV RNA displayed a sustained increase of at least 0.6 log10 copies/ml from the nadir value. In the first analysis, durability of response was analyzed with respect to baseline HIV RNA, HIV RNA at the nadir, and the drop in HIV RNA from baseline to the nadir. In the second analysis, time to rebound was examined using Kaplan-Meier analysis, stratifying by either baseline HIV RNA or HIV RNA at the nadir. RESULTS: In both analyses, the durability of response was not highly associated with either baseline RNA or the magnitude of RNA decline from baseline. Instead, a strong relationship was observed between the durability of response and the nadir plasma HIV-1 RNA value (P < 0.01). The nadir in viral load was generally reached after 12 weeks of randomized therapy. CONCLUSIONS: Viral RNA determinations at intermediate timepoints may be prognostic of impending virologic failure of protease inhibitor therapy. Therapeutic strategies that allow intensification of initial antiretroviral regimens in the subset of patients with incomplete virological response before the emergence of high level resistance should be investigated. 相似文献
123.
G Brix ME Bellemann U Haberkorn L Gerlach WJ Lorenz 《Canadian Metallurgical Quarterly》1996,23(7):897-906
The effective clinical use of the anticancer drug 5-fluorouracil (5-FU) requires the non-invasive assessment of its transport and metabolism, particularly in the tumor and the liver, where the drug is catabolized to alpha-fluoro-beta-alanine (FBAL). In this study, the potentials and limitations of dynamic 18F PET and metabolic 19F MRI examinations for noninvasive 5-FU monitoring were investigated in ACI and Buffalo rats with transplanted MH3924A and TC5123 Morris hepatomas, respectively. Selective 5-[19F]FU and [19F]FBAL MR images were acquired 5 and 70 min after 5-FU injection using a CHESS MRI sequence. After administration of 5-[18F]FU, the kinetics of the regional 5-[18F]FU uptake were measured by dynamic PET scanning over 120 min. To allow a comparison between PET and MRI data, standardized uptake values (SUV) were computed at the same points in time. The TC5123 hepatoma showed a significantly (p < 0.002) higher mean SUV at 5 and 70 min post-5-FU injection than the MH3924A cell lines, whereas there were no significant differences between the mean SUV measured in the liver of both animal populations. In contrast to the PET data, no significant differences in the mean 5-[19F]FU and [19F]FBAL MR signal values in the tumor of both models were observed. The MR images, however, yielded the additional information that 5-FU is converted to FBAL only in the liver and not in the hepatomas. 相似文献
124.
A model of the regulatory region of human decay accelerating factor (DAF) was built based on the known coordinates of a fragment of the structurally and functionally homologous serum protein, factor H. According to this model, the four short consensus repeats (SCRs) in DAF are arranged in a helical fashion. A positively charged surface area on SCRs 2 and 3, two of the three repeating units essential for function, is postulated to be the primary recognition site for the C3 convertases C4b2a and C3bBb. This area encompasses a cavity on SCR 2, as well as part of the groove on the SCR 2-SCR 3 interface. Two additional surface depressions are centered around the C-terminal disulfide bridges of SCRs 3 and 4. These are likely to provide additional ligand binding sites. Based on this model in conjunction with sequence homology to the Ba fragment of factor B, a mechanism of DAF's accelerated convertase decay action is postulated. 相似文献
125.
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127.
KL Houseknecht CA Baile RL Matteri ME Spurlock 《Canadian Metallurgical Quarterly》1998,76(5):1405-1420
Leptin, a 16-kDa protein secreted from white adipocytes, has been implicated in the regulation of food intake, energy expenditure, and whole-body energy balance in rodents and humans. The gene encoding leptin was identified by positional cloning and is the mutation leading to the profound obese phenotype of the ob/ob mouse. Exogenous administration of leptin to ob/ob mice leads to a significant improvement in reproductive and endocrine status as well as reduced food intake and weight loss. The expression and secretion of leptin is highly correlated with body fat mass and adipocyte size. Cortisol and insulin are potent stimulators of leptin expression, and expression is attenuated by beta-adrenergic agonists, cAMP, and thiazolidinediones. The role of other hormones and growth factors in the regulation of leptin expression and secretion is emerging. Leptin circulates specifically bound to proteins in serum, which may regulate its half-life and biological activity. Isoforms of the leptin receptor, members of the interleukin-6 cytokine family of receptors, are found in multiple tissues, including the brain. Many of leptin's effects on food intake and energy expenditure are thought to be mediated centrally via neurotransmitters such as neuropeptide Y. Multiple peripheral effects of leptin have also been recently described, including the regulation of insulin secretion by pancreatic beta cells and regulation of insulin action and energy metabolism in adipocytes and skeletal muscle. Leptin is thought to be a metabolic signal that regulates nutritional status effects on reproductive function. Leptin also plays a major role in hematopoeisis and in the anorexia accompanying an acute cytokine challenge. The profound effects of leptin on regulating body energy balance make it a prime candidate for drug therapies for humans and animals. 相似文献
128.
This study examined the relationships between social and demographic characteristics (ie, gender, race, year in school, desired residency choice, and socioeconomic background), motivations for entering the profession of podiatric medicine (extrinsic and intrinsic rewards), and negative attitudes toward treating elderly patients. The study used ordinary least squares multiple regression models to analyze data from a random, national sample of 448 podiatric medical students. In particular, the ordinary least squares models were developed to determine the independent effect of intrinsic and extrinsic rewards on negative attitudes toward treating elderly patients. Consistent with the study hypotheses, after adjusting for social and demographic characteristics, the study found extrinsic rewards to have strong positive relationships with negative attitudes toward treating elderly patients, and intrinsic rewards to have strong negative relationships with negative attitudes toward treating elderly patients. The authors discussed the implications of the findings for podiatric physicians and educators training podiatric medical students. 相似文献
129.
130.
Thin plasticized polymer films, poly(vinyl chloride) doped with a specific ion pairing quaternary ammonium compound, tridodecylmethylammonium chloride, and a lipophilic pH indicator, 3-hydroxy-4-(4-nitrophenylazo)phenyl octadeconate, are shown to exhibit significant and analytically useful optical response toward macromolecular heparin. The response mechanism is based on favorable extraction of heparin into the bulk organic film, owing to the specific ion-pairing complexation reaction between the quaternary ammonium species and the polyanion. A simultaneous coextraction of hydrogen ions results in protonation of the pH chromophore and hence a change in the optical absorbance of the polymeric film. When used in a limited volume/fixed exposure (10 min) detection mode, film absorbances change as a function of the initial heparin concentration in the range of 0.2-3.0 units/mL (1.2-18 micrograms/mL). The practical measurement response time is controlled by heparin diffusion through the stagnant diffusion layer adjacent to the surface of the film as well as within the bulk of the polymer film and is shown to increase with the molecular weight of the heparin species tested. No optical response to heparin is observed when a strong heparin complexing agent (e.g., protamine) is present in the test solution, suggesting that the polymer film can be used to conveniently monitor heparin-protamine (or other antagonist) titrations. The theory relating to the operation of the sensing film in either the equilibrium or the kinetic mode and the selectivity of the optimized film to heparin relative to small anions are presented. 相似文献