全文获取类型
收费全文 | 3007篇 |
免费 | 191篇 |
国内免费 | 93篇 |
专业分类
电工技术 | 206篇 |
综合类 | 111篇 |
化学工业 | 174篇 |
金属工艺 | 107篇 |
机械仪表 | 106篇 |
建筑科学 | 147篇 |
矿业工程 | 34篇 |
能源动力 | 43篇 |
轻工业 | 242篇 |
水利工程 | 56篇 |
石油天然气 | 45篇 |
武器工业 | 53篇 |
无线电 | 164篇 |
一般工业技术 | 133篇 |
冶金工业 | 1399篇 |
原子能技术 | 36篇 |
自动化技术 | 235篇 |
出版年
2024年 | 7篇 |
2023年 | 17篇 |
2022年 | 23篇 |
2021年 | 61篇 |
2020年 | 49篇 |
2019年 | 33篇 |
2018年 | 34篇 |
2017年 | 40篇 |
2016年 | 52篇 |
2015年 | 63篇 |
2014年 | 89篇 |
2013年 | 103篇 |
2012年 | 133篇 |
2011年 | 151篇 |
2010年 | 133篇 |
2009年 | 101篇 |
2008年 | 121篇 |
2007年 | 139篇 |
2006年 | 134篇 |
2005年 | 87篇 |
2004年 | 73篇 |
2003年 | 42篇 |
2002年 | 48篇 |
2001年 | 58篇 |
2000年 | 32篇 |
1999年 | 50篇 |
1998年 | 394篇 |
1997年 | 234篇 |
1996年 | 158篇 |
1995年 | 76篇 |
1994年 | 74篇 |
1993年 | 106篇 |
1992年 | 20篇 |
1991年 | 23篇 |
1990年 | 15篇 |
1989年 | 20篇 |
1988年 | 23篇 |
1987年 | 26篇 |
1986年 | 14篇 |
1985年 | 18篇 |
1984年 | 6篇 |
1983年 | 4篇 |
1982年 | 7篇 |
1981年 | 15篇 |
1980年 | 21篇 |
1978年 | 6篇 |
1977年 | 32篇 |
1976年 | 102篇 |
1975年 | 6篇 |
1955年 | 4篇 |
排序方式: 共有3291条查询结果,搜索用时 15 毫秒
221.
Binding and localization of the vasodilator and antitumor drug coactivator dipyridamole (DIP) and one of its derivatives, RA25, to phospholipid vesicles of DMPC (dimyristoylphosphatidylcholine) and DPPC (dipalmitoylphosphatidylcholine) was studied using fluorescence spectroscopy as well as quenching of fluorescence. The analysis of fluorescence data indicates that neutral dipyridamole binds to the phospholipids in their liquid crystalline phase with an association constant of 950 M(-1) and 1150 M(-1) to DMPC and DPPC, respectively. Protonation of DIP leads to a 3-fold reduction of the association constant. For the gel phospholipid phase, the binding is smaller (a factor of 2), independently of pH, suggesting that the more flexible lipid packing in the liquid crystalline phase facilitates the binding of the drug. The association constant of RA25 neutral form is considerably lower than for DIP, being around 295 M(-1). Fluorescence quenching with nitroxides TEMPO and stearic acid doxyl derivatives suggests the localization of DIP to be closer to the 5th carbon of alkyl chain. The quenching effect of 5-DSA below the lipid phase transition suggests that a strong static quenching may be operative. The quenching effect of 16-DSA is almost as great as that for 5-DSA below the phase transition, being even higher above the phase transition. This effect is probably due to the trans-gauche isomerization of the stearic acid nitroxide, making the encounter of its paramagnetic fragment with the DIP chromophore possible. Our data are consistent with DIP location close to the bilayer surface in the border of hydrophobic-polar heads interface which is similar to the data in micellar systems. In the case of RA25, the drug is in the outer part of the head group interface being much exposed to the aqueous phase and being significantly less accessible to the membrane nitroxide quenchers. 相似文献
222.
T Yoshikawa G Turner LE Esterling AR Sanders SD Detera-Wadleigh 《Canadian Metallurgical Quarterly》1997,2(5):393-397
Cerebral intraparenchymal cysts without communication with the ventricles are very rare. We report four such cases with no relevant past history or evidence of infection, haemorrhage, trauma, tumour or congenital neural tube defect. At operation smooth wailed cysts with an ependymal-type lining were found. To the best of our knowledge, we present the first correlation of their pathological and radiological features (including magnetic resonance imaging). We also review the literature on these cysts. 相似文献
223.
GL Burke DE Bild JE Hilner AR Folsom LE Wagenknecht S Sidney 《Canadian Metallurgical Quarterly》1996,1(4):327-335
Copper/zinc (Cu/ZnSOD) and manganese (MnSOD) superoxide dismutases which catalyze the dismutation of toxic superoxide anion, O(2-)-, to O2 and H2O2, play a major role in protecting cells from toxicity of oxidative stress. However, cells overexpressing either form of the enzyme show signs of toxicity, suggesting that too much SOD may be injurious to the cell. To elucidate the possible mechanism of this cytotoxicity, the effect of SOD on DNA and RNA strand scission was studied. High purity preparations of Cu/ZnSOD and MnSOD were tested in an in vitro assay in which DNA cleavage was measured by conversion of phage phi X174 supercoiled double-stranded DNA to open circular and linear forms. Both types of SOD were able to induce DNA strand scission generating single- and double-strand breaks in a process that required oxygen and the presence of fully active enzyme. The DNA strand scission could be prevented by specific anti-SOD antibodies added directly or used for immunodepletion of SOD. Requirement for oxygen and the effect of Fe(II) and Fe(III) ions suggest that cleavage of DNA may be in part mediated by hydroxyl radicals formed in Fenton-type reactions where enzyme-bound transition metals serve as a catalyst by first being reduced by superoxide and then oxidized by H2O2. Another mechanism was probably operative in this system, since in the presence of magnesium DNA cleavage by SOD was oxygen independent and not affected by sodium cyanide. It is postulated that SOD, by having a similar structure to the active center of zinc-containing nucleases, is capable of exhibiting non-specific nuclease activity causing hydrolysis of the phosphodiester bonds of DNA and RNA. Both types of SOD were shown to effectively cleave RNA. These findings may help explain the origin of pathology of certain hereditary diseases genetically linked to Cu/ZnSOD gene. 相似文献
224.
LE Shields SB Uhrich CA Komarniski MH Wener TC Winter 《Canadian Metallurgical Quarterly》1996,15(11):735-739
The purpose of this retrospective study was to evaluate the utility of routine measurement of amniotic fluid alpha-fetoprotein levels at the time of second trimester genetic amniocentesis (mean gestational age, 17.3 weeks +/- 2.5 weeks standard deviation; median, 16.8 weeks; range, 15 to 22 weeks). During the study period 7174 patients underwent second trimester genetic amniocentesis. Outcome data were available in all cases. In 79 (1.1%) cases the amniotic fluid alpha-fetoprotein level was > or = 2.0 multiples of the median. Thirty-three of the 79 (42%) patients had normal ultrasonograms, and in 31 of 33 (94%) the amniotic fluid alpha-fetoprotein level was between 2.0 and 3.0 multiples of the median. Forty-six of the 79 (58%) patients had abnormal ultrasonographic findings, and of these, 82% were neural tube defects, abdominal wall defects, or cystic hygromas. Acetylcholinesterase was positive in 37 cases, all of which had abnormal ultrasonographic findings. None of the fetuses with negative findings on sonographic screening had detectable abnormalities at birth. In this study, with over 7000 patients, amniotic fluid alpha-fetoprotein and acetylcholinesterase levels did not increase the detection of fetal abnormalities. On the basis of these results, routine measurement of amniotic fluid alpha-fetoprotein level at the time of routine genetic amniocentesis (15 to 22 weeks) does not appear justified. 相似文献
225.
NJ Meropol M Porter LE Blumenson MJ Lindemann RP Perez L Vaickus GM Loewen PJ Creaven KA Wilkes MA Giedlin MA Caligiuri 《Canadian Metallurgical Quarterly》1996,2(4):669-677
We aimed to determine the toxicity and immunological effects of daily s.c. administered low-dose interleukin (IL) 2. Adult cancer patients received a single daily s.c. injection of IL-2 as outpatients for 90 consecutive days. Cohorts of four to nine patients were treated at escalating IL-2 dose levels until the maximum tolerated dose (MTD) was defined. Peripheral blood mononuclear cell phenotyping, IL-2 serum levels, and the presence of anti-IL-2 antibodies were investigated. Thirty-eight patients were treated at seven IL-2 dose levels ranging from 0.4 to 1.75 million International Units (mIU)/m2 daily. The MTD was 1.25 mIU/m2, with constitutional side effects, vomiting, and hyperglycemia dose limiting. Severe toxicity did not occur at or below the MTD, although mild local skin reaction and mild constitutional side effects were common. Objective tumor regressions were not observed during this Phase I trial. Low-dose IL-2 resulted in natural killer (NK) cell (CD3(-) CD56(+)) expansion at all dose levels. This effect was dose dependent (P < 0.01), ranging from a 154 to 530% increase over baseline. Peak NK levels were achieved at 6-8 weeks and sustained through 12 weeks of therapy. As predicted by in vitro studies of IL-2 receptor structure-activity relationships, the subset of NK cells that constitutively express high-affinity IL-2 receptors (CD3(-)CD56(bright+)) showed more profound dose-dependent expansion, with increases ranging from 368 to 2763% (P = 0.015). NK expansion occurred at peak IL-2 levels <10 pM (2.3 IU/ml). Three patients developed nonneutralizing anti-IL-2 antibodies. Thus, we concluded that selective expansion of NK cells may be achieved in vivo with daily s.c. injections of low-dose IL-2 with minimal toxicity. 相似文献
226.
In hippocampal neurons, neurotransmitter release can be regulated by protein kinase A (PKA) through a direct action on the secretory machinery. To identify the site of PKA modulation, we have taken advantage of the ability of the neurotoxin Botulinum A to cleave the synaptic protein SNAP-25. Cleavage of this protein decreases the Ca2+ responsiveness of the secretory machinery by partially uncoupling Ca2+-sensing from fusion per se. This is expressed as a shift toward higher Ca2+ levels of the Ca2+ to neurotransmitter release relationship and as a perturbation of synaptic delay under conditions where secretion induced by the Ca2+-independent secretagogue ruthenium red is unimpaired. We find that SNAP-25 cleavage also perturbs PKA-dependent modulation of secretion; facilitation of ruthenium red-evoked neurotransmitter release by the adenylyl cyclase activator forskolin is blocked completely after Botulinum toxin A action. Together with our observation that forskolin modifies the Ca2+ to neurotransmitter release relationship, our results suggest that SNAP-25 acts as a functional linker between Ca2+ detection and fusion and that PKA modulates an early step in the secretory machinery related to calcium sensing to facilitate synaptic transmission. 相似文献
227.
228.
229.
JM Ding GF Buchanan SA Tischkau D Chen L Kuriashkina LE Faiman JM Alster PS McPherson KP Campbell MU Gillette 《Canadian Metallurgical Quarterly》1998,394(6691):381-384
Circadian clocks are complex biochemical systems that cycle with a period of approximately 24 hours. They integrate temporal information regarding phasing of the solar cycle, and adjust their phase so as to synchronize an organism's internal state to the local environmental day and night. Nocturnal light is the dominant regulator of this entrainment. In mammals, information about nocturnal light is transmitted by glutamate released from retinal projections to the circadian clock in the suprachiasmatic nucleus of the hypothalamus. Clock resetting requires the activation of ionotropic glutamate receptors, which mediate Ca2+ influx. The response induced by such activation depends on the clock's temporal state: during early night it delays the clock phase, whereas in late night the clock phase is advanced. To investigate this differential response, we sought signalling elements that contribute solely to phase delay. We analysed intracellular calcium-channel ryanodine receptors, which mediate coupled Ca2+ signalling. Depletion of intracellular Ca2+ stores during early night blocked the effects of glutamate. Activators of ryanodine receptors induced phase resetting only in early night; inhibitors selectively blocked delays induced by light and glutamate. These findings implicate the release of intracellular Ca2+ through ryanodine receptors in the light-induced phase delay of the circadian clock restricted to the early night. 相似文献
230.
GM Rossolini S Schippa ML Riccio F Berlutti LE Macaskie MC Thaller 《Canadian Metallurgical Quarterly》1998,54(8):833-850
Bacterial nonspecific acid phosphohydrolases (NSAPs) are secreted enzymes, produced as soluble periplasmic proteins or as membrane-bound lipoproteins, that are usually able to dephosphorylate a broad array of structurally unrelated substrates and exhibit optimal catalytic activity at acidic to neutral pH values. Bacterial NSAPs are monomeric or oligomeric proteins containing polypeptide components with an M(r) of 25-30 kDa. On the basis of amino acid sequence relatedness, three different molecular families of NSAPs can be distinguished, indicated as molecular class A, B and C, respectively. Members of each class share some common biophysical and functional features, but may also exhibit functional differences. NSAPs have been detected in several microbial taxa, and enzymes of different classes can be produced by the same bacterial species. Structural and phyletic relationships exist among the various bacterial NSAPs and some other bacterial and eucaryotic phosphohydrolases. Current knowledge on bacterial NSAPs is reviewed, together with analytical tools that may be useful for their characterization. An overview is also presented concerning the use of bacterial NSAPs in biotechnology. 相似文献