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991.
A release of radio-immunoassayable LHRH from the stalk-median eminence of neonatal piglets and prepubertal gilts was measured using an in vitro incubation system. The stalk-median eminence was collected from one-week-old male (n = 19) and female (n = 21) piglets and from 6-month-old prepubertal ovariectomized gilts given oestradiol benzoate (20 micrograms/kg b.w.; n = 52) or left untreated (control; n = 25) 30 or 68 h before slaughter. Each vial, containing the stalk-median eminence in 2 ml of Krebs-Ringer bicarbonate buffer, was incubated for 30 min, followed by 30 min incubations during which either basal release or the effect of adrenoreceptor antagonists and agonists on LHRH output was evaluated. There were no differences between the basal release of LHRH (x +/- SEM; pg/ml) from the stalk-median eminence of male (65.5 +/- 9.8) and female (66.3 +/- 9.6) newborn piglets. The addition of propranolol (10(-6) M) caused a 250% increase in LHRH release from the stalk-median eminence explants of neonatal males (p = 0.08) and females (p < 0.05). Neither norepinephrine nor phentolamine affected LHRH release from the stalk-median eminence of newborn males and females. The basal release of LHRH (pg/ml) from the stalk-median eminence explants collected from ovariectomized gilts given oestradiol benzoate 30 and 68 h before slaughter or left untreated was similar (147.5 +/- 36.1, 236.4 +/- 77.7 and 202.0 +/- 41.6, respectively). Propranolol evoked a significant increase in LHRH secretion from the stalk-median eminence in the control group, but not in the groups given oestradiol benzoate. Norepinephrine (10(-6) M) increased LHRH release from the stalk-median eminence collected from the control animals, 30 h and 68 h after oestradiol benzoate treatment by 48, 78 and 73 percent, respectively. Phentolamine (10(-6) M) did not affect LHRH release from the stalk-median eminence in control animals and ovariectomized gilts primed with oestradiol benzoate. Urapidil (10(-6) M, alpha 1-adrenoreceptor antagonist) did not affect the basal LHRH release from the stalk-median eminence of gilts from the control group and group slaughtered 30 h after oestradiol benzoate treatment, but caused a rapid increase of LHRH release from the stalk-median eminence 68 h after oestradiol benzoate treatment. Phenylephrine (10(-6) M) did not affect LHRH output from the stalk-median eminence collected at various time periods after oestradiol benzoate administration in vivo. These results suggest that in pigs, nerve terminals releasing LHRH at the stalk-median eminence level are sensitive to adrenergic stimulation or inhibition and that the adrenergic system can be modulated by estrogens in the prepubertal gilts. 相似文献
992.
A Alamir DF Middendorf P Baker NS Nahman AB Fontaine LA Hebert 《Canadian Metallurgical Quarterly》1997,30(6):851-855
Considerable evidence indicates that the microvascular changes observed in psoriasis are a result of angiogenesis. Vascular proliferation is driven by the local production of molecules which have angiogenic activity. Platelet-derived endothelial cell growth factor/thymidine phosphorylase (PDECGF/TP) is a potent angiogenic factor active in in vivo angiogenesis assays and overexpressed in several tumour types. We have demonstrated by ribonuclease protection analysis a consistently high degree of PDECGF/TP mRNA production in lesional psoriatic skin, while immunohistochemical studies revealed strong PDECGF/TP immunoreactivity in lesional epidermis, with nuclear staining present in basal keratinocytes and cytoplasmic immunoreactivity in suprabasal layers. Non-lesional skin showed minimal PDECGF/TP mRNA production and weak epidermal immunostaining. These results indicate a potential role for PDECGF/TP in the pathophysiology of psoriasis, and reveal a target for antiangiogenesis therapy in the treatment of this disease. 相似文献
993.
994.
DH Wang K Ishii E Seno S Yane T Horike H Yamamoto N Suganuma M Arimichi K Taketa 《Canadian Metallurgical Quarterly》1998,36(1):14-19
The practice of withdrawing blood samples for activated partial thromboplastin time (aPTT) analysis from heparinized arterial lines may result in inaccurate aPTT values. The purpose of this study was to compare venous aPTT values to aPTT values withdrawn from heparinized arterial lines in children. The author suggests a method of obtaining accurate aPTT values using a specified discard volume. 相似文献
995.
Magnesium is the fourth most abundant metal found in the body. It plays a crucial role in numerous biological processes. It is a natural calcium antagonist. New experimental data suggest that Mg+2 influences a variety of lung structures. Intracellular Mg+2 is thought to modulate smooth muscle contractions and it is known to have a direct effect on calcium uptake, resulting in smooth muscle relaxation. Magnesium has been forgotten cation from the therapeutical point of view, but now several clinical reports point to the salutary actions of Mg+2 in various lung diseases. Many reports suggests that magnesium sulfate and aspartate has certainly a role as an adjunct to traditional therapy in asthma and asthma-like conditions and have been helpful in the treatment of acute exacerbations of asthma. 相似文献
996.
Malignant mesothelioma (MM) is a fatal malignancy refractory to all forms of standard anticancer therapy. This article reports the results of a phase I clinical trial assessing the safety of intrapleural delivery and efficacy of intratumoral gene transfer of recombinant adenovirus (rAd) containing herpes simplex virus thymidine kinase (HSVtk) gene into the pleural space of patients with MM, followed by systematic treatment with the antiviral drug ganciclovir (GCV) for 14 days. AD.RSVtk/GCV gene therapy proved to be well tolerated, with evidence of significant gene transfer particularly at high vector doses and with elimination of preliminary biopsy. Ongoing gene therapy trials for mesothelioma at two other centers, focusing on immunostimulation and using suicide gene therapy as a tumor vaccine, are also reviewed in this article. 相似文献
997.
998.
In several animal models, preliminary studies have indicated that pantethine may inhibit cataract formation. Therefore, preclinical trials need to be conducted to study the pharmacology of pantethine in the ocular lens and to establish its efficacy. Since pantethine, which is a disulfide, can undergo a variety of chemical modifications such as reduction and formation of mixed disulfides, a detailed study was first conducted to determine the stability of pantethine in rabbit lens homogenate. A knowledge of the stability of pantethine in lens homogenate was necessary to establish if pantethine could be metabolized in the time it takes to harvest and homogenize a lens. The results of this study will be used to establish a protocol for harvesting and homogenizing lens samples. Pantethine (100 microM) is completely reduced to pantetheine in rabbit lens homogenate in about 16 min. About 1.5% of the pantethine added to lens homogenate forms a mixed disulfide with lens proteins, and the remainder is found in the supernatant. The supernatant pantethine concentration decreases exponentially as a function of time, and the terminal half-life for this process is 3.3 min. The free supernatant pantetheine concentration increases in pseudo first order manner as a function of time with a rate constant of 4.3 min. Pantethinase activity is not significant, because the free supernatant pantetheine concentration did not decrease. The exact mechanism of pantethine reduction in rabbit lens homogenate remains to be determined. 相似文献
999.
AM Orville N Elango JD Lipscomb DH Ohlendorf 《Canadian Metallurgical Quarterly》1997,36(33):10039-10051
Protocatechuate 3,4-dioxygenase (3,4-PCD) catalyzes the oxidative ring cleavage of 3,4-dihydroxybenzoate to produce beta-carboxy-cis, cis-muconate. Crystal structures of Pseudomonas putida3,4-PCD [quaternary structure of (alphabetaFe3+)12] complexed with seven competitive inhibitors [3-hydroxyphenylacetate (MHP), 4-hydroxyphenylacetate (PHP), 3-hydroxybenzoate (MHB), 4-hydroxybenzoate (PHB), 3-fluoro-4-hydroxybenzoate (FHB), 3-chloro-4-hydroxybenzoate (CHB), and 3-iodo-4-hydroxybenzoate (IHB)] are reported at 2.0-2.2 A resolution with R-factors of 0. 0.159-0.179. The inhibitors bind in a narrow active site crevasse lined with residues that provide a microenvironment that closely matches the chemical characteristics of the inhibitors. This results in as little as 20% solvent-exposed surface area for the higher-affinity inhibitors (PHB, CHB, and FHB). In uncomplexed 3,4-PCD, the active site Fe3+ is bound at the bottom of the active site crevasse by four endogenous ligands and a solvent molecule (Wat827). The orientations of the endogenous ligands are relatively unperturbed in each inhibitor complex, but the inhibitors themselves bind to or near the iron in a range of positions, all of which perturb the position of Wat827. The three lowest-affinity inhibitors (MHP, PHP, and IHB) yield distorted trigonal bipyramidal iron coordination geometry in which the inhibitor C4-phenolate group displaces the solvent ligand. MHB binds within the active site, but neither its C3-OH group nor the solvent molecule binds to the iron. The C4-phenolate group of the three highest-affinity inhibitors (PHB, CHB, and FHB) coordinates the Fe3+ adjacent to Wat827, resulting in a shift in its position to yield a six-coordinate distorted octahedral geometry. The range of inhibitor orientations may mimic the mechanistically significant stages of substrate binding to 3, 4-PCD. The structure of the final substrate complex is reported in the following paper [Orville, A. M., Lipscomb, J. D., & Ohlendorf, D. H. (1997) Biochemistry 36, 10052-10066]. 相似文献
1000.
BACKGROUND: Metabolic drug-drug interactions can occur between drugs that are substrates or inhibitors of the same cytochrome P450 (CYP) isoenzymes, but can be prevented by knowing which isoenzymes are primarily responsible for a drug's metabolism. m-Chlorophenylpiperazine (mCPP) is a psychopharmacologically active metabolite of four different psychiatric drugs. The present experiments were designed to identify the CYP isoenzymes involved in the metabolism of mCPP to its main metabolite p-hydroxy-mCPP (OH-mCPP). METHODS: The rate of production of OH-mCPP from mCPP was correlated with isoform activities in a panel of human liver microsomes, was assessed using a panel of individual complementary DNA-expressed human CYP isoenzymes, and was investigated in the presence of a specific inhibitor of CYP2D6. RESULTS: OH-mCPP production correlated significantly with CYP2D6 activity in human liver microsomes. Furthermore, incubations with microsomes from cells expressing CYP2D6 resulted in OH-mCPP formation, whereas no mCPP was formed from incubations with microsomes from cells expressing other individual isoforms. Finally, when the specific CYP2D6 inhibitor quinidine was preincubated with either human liver microsomes or cells expressing human CYP2D6, there was a concentration-dependent decrease in the production of OH-mCPP. CONCLUSIONS: These results confirm that CYP2D6 is the isoform responsible for the p-hydroxylation of mCPP, and indicate that caution should be exercised in coprescribing inhibitors or substrates of CYP2D6 with drugs that have mCPP as a metabolite. 相似文献