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941.
After 4 hours of treatment with TNF, newly synthesized endothelial leukocyte adhesion molecule 1, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1 molecules are diffusely expressed on the apical surface of cultured umbilical vein endothelial cells. Such cells maintain the epithelioid, cobblestone appearance of untreated endothelial cells and display cytoskeletal actin largely arranged in dense peripheral bands. After 24 to 72 hours of treatment with TNF, cells become elongated and rearrange their actin filaments into longitudinal stress fibers. At this time, intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 remain elevated but redistribute to the cell junctions. Intercellular adhesion molecule 2, beta 1 integrins, and beta 3 integrins also redistribute to cell junctions in TNF-treated cultures. IFN-gamma produces morphologic changes similar to those induced by TNF but does not cause surface protein redistribution. Cells treated with TNF plus IFN-gamma become even more elongated and display TNF-like redistributions. We conclude that TNF activates a program of membrane protein redistribution, and we speculate that this dynamic redistribution of adhesion molecules to cell junctions may contribute to the recruitment of leukocytes to sites of inflammation.  相似文献   
942.
Experimental autoimmune encephalomyelitis (EAE) is a CD4+ Th1-mediated demyelinating disease of the central nervous system that serves as a model for multiple sclerosis (MS). There are several considerations that suggest a role for chemokines in the disease process. First, chemokines are highly expressed in the central nervous system with a tight temporal relationship to disease activity. Second, in vivo neutralization studies showed a distinct role for specific chemokines in the evolution of the process. Third, the selective and differential expression of chemokines in differing models of EAE bears a close relationship to the patterns of inflammatory pathology. Fourth, the spatial distribution of chemokine expression could plausibly contribute to lesion architecture. Finally, preliminary observations in MS material suggest that chemokine expression observed in EAE may provide useful information regarding the pathogenesis of inflammation in MS. We propose that temporal and spatial expression of chemokines are crucial factors, complementing adhesion molecule up-regulation, that regulate EAE disease activity.  相似文献   
943.
1. Previous work from this laboratory has shown that rostral nucleus tractus solitarii (rNTS) neurons can be separated into four different classes on the basis of responses to a current injection paradigm consisting of membrane hyperpolarization immediately followed by a depolarizing pulse. These classes have been termed Group I, II, III, and IV neurons. The regular repetitive firing discharge pattern of Group I cells is changed into an irregular spike train by membrane hyperpolarization. Hyperpolarization of Group II neurons delays the firing discharge induced by depolarization. Hyperpolarization had the least effect on the discharge pattern of Group III neurons. The discharge pattern of Group IV neurons consisted of a short burst of spikes. We used whole-cell recordings and pharmacological channel blockers in an in vitro brain stem slice preparation to determine the ionic basis for the repetitive firing properties of rNTS neurons. 2. Application of 4-aminopyridine (4-AP, 1 mM) decreased input resistance and increased action potential duration in all groups of neurons. However, the discharge pattern of Group I, III, and IV neurons was either unaltered or slightly modified by 4-AP. In contrast the delay in firing of Group II cells induced by hyperpolarization was strongly reduced and in some cases completely suppressed by application of 4-AP. This suggests that a 4-AP-sensitive conductance primarily underlies the firing pattern of Group II cells. 3. Voltage-clamp recordings revealed that the delay in Group II neurons is due to a transient outward potassium current that is partially inactivated around the resting membrane potential. Hyperpolarization removed this inactivation, causing a delay in the firing of the cell. The potassium current was blocked by 4-AP. A similar current was occasionally seen in neurons of the other groups. On the basis of its voltage and pharmacological dependence this current was presumed to be an A-current (IKA). 4. Blockade of calcium currents by a low-calcium (0.5 mM) saline containing 2 mM Co2+ depressed the excitability of rNTS cells. For Group II neurons the delay in firing activity was increased. In the other groups the repetitive firing pattern was suppressed. In addition the amplitude of the afterhyperpolarization occurring after a short train of action potentials was substantially reduced. This indicates that calcium currents (ICa) and calcium-activated potassium currents (IKCa) contribute to the repetitive firing properties of rNTS neurons. 5. In about half of Group I, III, and IV neurons an additional property was found.(ABSTRACT TRUNCATED AT 400 WORDS)  相似文献   
944.
945.
STUDY OBJECTIVE: Accurate diagnosis in emergency department patients with possible myocardial ischemia is problematic. Two-dimensional echocardiography has a high sensitivity for identifying patients with myocardial infarction (MI); however, few studies have investigated its diagnostic ability when used acutely in ED patients with possible myocardial ischemia. Therefore we investigated the ability of ED echocardiography for predicting cardiac events in patients with possible myocardial ischemia. METHODS: Echocardiography was performed within 4 hours of ED presentation in 260 patients with possible myocardial ischemia, and was considered positive if there were segmental wall motion abnormalities or the ejection fraction was less than 40%. ECGs were considered abnormal if there was an ST-segment elevation or depression of greater than or equal to 1 mm, or ischemic T-wave inversion. Cardiac events included MI and revascularization. RESULTS: Of the 260 patients studied, 45 had cardiac events (23 MI, 19 percutaneous transluminal angioplasty, 3 coronary bypass surgery). The sensitivity of echocardiography for predicting cardiac events was 91% (95% confidence interval 79% to 97%]), which was significantly higher than the ECG (40% [95% CI 27% to 55%]: P < .0001), although specificity was lower (75% [95% CI 69% to 81%] versus 94% [95% CI 90% to 97%]; P < .001). Addition of the echocardiography results to baseline clinical variables and the ECG added significant incremental diagnostic value (P < .001). With use of multivariate analysis, only male gender (P < .03, odds ratio [OR] 2.4 [1.1 to 5.3]), and a positive echocardiographic finding (P < .0001, OR 24 [9 to 65]) predicted cardiac events. Excluding patients with abnormal ECGs (N = 30) did not affect sensitivity (85%) or specificity (74%) of echocardiography. CONCLUSION: Echocardiography performed in ED patients with possible myocardial ischemia identifies those who will have cardiac events, is more sensitive than the ECG, and has significant incremental value when added to baseline clinical variables and the ECG.  相似文献   
946.
This article reports results from a meta-analysis on adult age differences in the negative priming effect (21 studies on identity negative priming and 8 on location negative priming). Both younger and older adults were found to be susceptible to the negative priming effect in identity and location tasks. Effect sizes were homogeneous for both tasks, indicating that the data are adequately described without reference to moderator variables. State trace analysis on identity tasks, in which mean latencies in negative priming conditions were regressed onto mean latencies in baseline conditions, showed (a) that in both age groups the negative priming effect is proportional rather than additive and (b) that the negative priming effect is smaller in older adults as compared with younger adults.  相似文献   
947.
From January 1988 to November 1992, 107 (3.5%) of 3074 postneonatal children admitted to the Children's Emergency Room, University of Maiduguri Teaching Hospital, Nigeria, had sporadic pyogenic meningitis; 66 (61.7%) were aged < or = 12 months. Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae together were responsible for 77.3% (58) of 75 culture-proven cases, 13.4% (10) had Enterobacteriaceae, 5.3% (4) had Staphylococcus aureus and 4% (3) untyped alpha-haemolytic streptococci. Fifty percent of 62 bacteria were resistant to ampicillin, 47.2% of 36 to penicillin and 10.7% of 56 to chloramphenicol; none of 21 bacteria was simultaneously resistant to all three antibiotics. Up until 1992, we have encountered treatment failure with a regimen containing chloramphenicol in only 2 of 53 patients; the 2 patients had coliform meningitis. Non-meningococcal bacteria are an important cause of sporadic pyogenic meningitis in sub-Saharan Nigeria and chloramphenicol is the most appropriate initial drug of choice at the present time for the management of sporadic meningitis.  相似文献   
948.
We have examined the formation of 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxodG) in reactions of peroxynitrite with 2'-deoxyguanosine (dG) and calf-thymus DNA. Peroxynitrite reacts with dG at neutral pH, but this reaction does not result in the buildup of 8-oxodG. We also do not find any evidence for the formation of 8-oxodG in calf-thymus DNA upon exposure to peroxynitrite. When 8-oxodG is mixed with 1000-fold excess dG and then allowed to react with peroxynitrite, about 50% of the 8-oxodG is destroyed. The preferential reaction of 8-oxodG is also evident when dG in calf-thymus DNA is partially oxidized in an Udenfriend system and then allowed to react with peroxynitrite. We suggest that 8-oxodG is not produced in peroxynitrite-mediated oxidations of dG and DNA or that it is produced but then is rapidly consumed in further reactions with peroxynitrite. Oxidized DNA bases frequently can be more oxidation sensitive than their corresponding progenitors and, therefore, may be present at] low steady-state concentrations and not represent stable markers of oxidative stress status. The importance of the 8-oxodG/peroxynitrite reaction is discussed in relation to the formation of more stable, secondary oxidation products that might be more useful markers of DNA damage.  相似文献   
949.
Various in vitro studies have shown that delta-9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana, has a variety of inhibitory effects on immune functions including effects on macrophages. The present studies have examined the mechanism of THC's effects on tumor necrosis factor alpha (TNF-alpha), a major macrophage-produced cytokine and an important mediator involved in cytokine networks and in host defense mechanisms. Exposure of macrophages to medium containing THC has resulted in low levels of soluble TNF-alpha protein and reduced TNF-alpha bioactivity in the culture supernatant. However, THC did not inhibit the levels of LPS-induced TNF-alpha mRNA and intracellular TNF-alpha precursor protein, had only a weak effect on expression of membrane-bound TNF-alpha, but suppressed TNF-alpha maturation/secretion by macrophages. The higher the THC concentration in the medium during TNF-alpha induction, the greater the amount of intracellular TNF-alpha precursors that accumulated in the activated macrophages and the less mature TNF-alpha was released from the cells. Data suggest that TNF-alpha production by macrophages was altered greatly by exposure to THC at the levels of TNF-alpha precursor maturation and secretion.  相似文献   
950.
To explore factors associated with longevity, we studied geographic distribution of centenarians in Japan, based on 1990 the population census. We calculated the proportion of centenarians from ratio of number of centenarian to that of population aged 65 years or older. Centenarians in Japan consisted of number 4,152 persons. By prefecture, Tokyo had the most centenarians (383), followed by Okinawa (193) and Fukuoka (151) prefectures. Fukui had the least (24), followed by Akita (26) and Ishikawa (29) prefectures. The proportion of centenarians in Japan was 21.6 (per 100,000 populations) in 1990. By prefecture, the highest proportion lived in Okinawa (133.8), whereas the fewest were found in Akita (8.9). The relationship between geographic distribution of centenarians and environmental factors and nutritional factors were analyzed. Correlation coefficients between proportion of centenarians and mean temperature, high quality of welfare work and of medical services, and having much leisure time were positively significant. As for nutritional factor, correlation coefficients between proportion of centenarians and protein (% of energy) was positively significant, while intake of total energy was negatively significant.  相似文献   
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