全文获取类型
收费全文 | 4797篇 |
免费 | 264篇 |
国内免费 | 149篇 |
专业分类
耳鼻咽喉 | 11篇 |
儿科学 | 65篇 |
妇产科学 | 15篇 |
基础医学 | 715篇 |
口腔科学 | 53篇 |
临床医学 | 269篇 |
内科学 | 647篇 |
皮肤病学 | 41篇 |
神经病学 | 912篇 |
特种医学 | 65篇 |
外科学 | 181篇 |
综合类 | 442篇 |
现状与发展 | 1篇 |
预防医学 | 176篇 |
眼科学 | 32篇 |
药学 | 1229篇 |
中国医学 | 258篇 |
肿瘤学 | 98篇 |
出版年
2023年 | 28篇 |
2022年 | 50篇 |
2021年 | 105篇 |
2020年 | 81篇 |
2019年 | 97篇 |
2018年 | 83篇 |
2017年 | 96篇 |
2016年 | 104篇 |
2015年 | 115篇 |
2014年 | 226篇 |
2013年 | 291篇 |
2012年 | 254篇 |
2011年 | 262篇 |
2010年 | 191篇 |
2009年 | 236篇 |
2008年 | 244篇 |
2007年 | 263篇 |
2006年 | 179篇 |
2005年 | 168篇 |
2004年 | 150篇 |
2003年 | 139篇 |
2002年 | 125篇 |
2001年 | 106篇 |
2000年 | 83篇 |
1999年 | 76篇 |
1998年 | 74篇 |
1997年 | 96篇 |
1996年 | 78篇 |
1995年 | 81篇 |
1994年 | 70篇 |
1993年 | 67篇 |
1992年 | 75篇 |
1991年 | 60篇 |
1990年 | 92篇 |
1989年 | 79篇 |
1988年 | 61篇 |
1987年 | 50篇 |
1986年 | 52篇 |
1985年 | 77篇 |
1984年 | 70篇 |
1983年 | 43篇 |
1982年 | 55篇 |
1981年 | 60篇 |
1980年 | 50篇 |
1979年 | 35篇 |
1978年 | 26篇 |
1977年 | 20篇 |
1976年 | 18篇 |
1974年 | 12篇 |
1973年 | 18篇 |
排序方式: 共有5210条查询结果,搜索用时 15 毫秒
21.
Roland Seifert Rahel Burde Günter Schultz 《Naunyn-Schmiedeberg's archives of pharmacology》1989,340(1):101-106
Summary There are controversial reports in the literature concerning the effects of opioids on superoxide (O
2
–
) formation in phagocytes, these agents being either inhibitory or stimulatory. We re-examined this issue and compared the effects of the Chemotactic peptide, N-formyl-l,-methionyl-l-leucyl-l-phenylalanine (fMet-Leu-Phe), phorbol myristate acetate (PMA), ATP, platelet activating factor (PAF), cytochalasin B (CB) and prostaglandin E1 (PGE1) with those of various opioids on O
2
–
formation in human neutrophils and HL-60 leukemic cells under defined experimental conditions. In the presence of CB, fMet-Leu-Phe and PAF concentration-dependently activated O
2
–
formation in neutrophils with EC50 values of 20 nM and 100 nM, respectively. In the absence of CB, fMet-Leu-Phe and PAF were much less effective. PAF synergistically enhanced O
2
–
formation induced by fMet-Leu-Phe. ATP at a concentration of 100 M and the opioids, methionine enkephalin, -endorphin, dynorphin, [d-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin, [d-Ala2-d-Leu5]-enkephalin and morphine at concentrations between 10 pM to 1 M did not activate O
2
–
formation. ATP but not \-endorphin potentiated fMet-Leu-Phe-induced O
2
–
formation. O
2
–
formation induced by a maximally stimulatory concentration of PMA (100 ng/ml) was enhanced by fMet-Leu-Phe but was unaffected by methionine enkephalin or PGE1. PMA at a non-stimulatory concentration (2 ng/ml) potentiated the effect of fMet-Leu-Phe but did not induce responsiveness to PAF, ATP or -endorphin. PGE1 strongly inhibited fMet-Leu-Phe-induced O
2
–
formation, whereas morphine, methionine enkephalin and the opioid antagonist, naloxone, were without effect. In HL-60 cells differentiated with dibutyryl cAMP, fMet-Leu-Phe, PAF and ATP but not -endorphin activated O
2
–
formation. Our results show that O
2
–
formation is differentially regulated by various classes of intercellular signal molecules and that opioids do not play a role in the regulation of O
2
–
formation. The precise definition of the experimental conditions and control experiments with established modulators of O
2
–
formation are essential to evaluate the role of opioids in the regulation of this effector system.Send offprint requests to R. Seifert at the above address 相似文献
22.
M. W. Warenycia K. A. Smith C. S. Blashko S. B. Kombian R. J. Reiffenstein 《Archives of toxicology》1989,63(2):131-136
Administration of sodium hydrosulfide (NaHS), an alkali salt of hydrogen sulfide (H2S) at doses of 10 and 30 mg/kg, corresponding to sublethal and lethal doses (0.66 and 2.0 X LD50) resulted in significant increases in regional catecholamine levels of the rat brain only after the dose of 2.0 × LD50 of NaHS. Whereas the cortex and the cerebellum showed little or no change in catecholamine content, the hippocampus, striatum and brainstem all showed increases in noradrenaline and adrenaline. Additional analysis also showed that brainstem dopamine and 5-hydroxytryptamine levels (5-HT) increased as well. In vitro testing of sulfide for inhibition of monoamine oxidase (MAO) activity showed the anion to be inhibitory with an IC50 of 39.1±3.6 M. Inhibition of MAO activity ex vivo could be demonstrated at a dose of 100 mg/kg but not at the lower dose of 30 mg/kg NaHS. Inhibition of enzyme activity could not be demonstrated at this lower dose, possibly due to the well known rapid intramitochondrial metabolism of sulfide. Correlation of synaptosomal and mitochondrial sulfide levels with enzyme inhibition data suggests that inhibition of MAO may be an important contributing factor to the mechanism(s) underlying loss of central respiratory drive after fatal intoxication with H2S. 相似文献
23.
In vitro experiments were performed on brainstem – spinal cord preparations from mouse neonates to compare the noradrenergic regulations of the respiratory network in the control C3H/HeJ strain and the transgenic Tg8 strain which has been created from the C3H/HeJ strain by deletion of the gene encoding monoamine oxidase A (MAOA), the main enzyme for serotonin degradation. In both control and MAOA-deficient strains, we show: (i) that the pontine A5 area exerts a potent inhibitory modulation on the respiratory rhythm generator; (ii) that noradrenaline application induces a tonic phrenic activity; and (iii) that noradrenaline increases the respiratory rhythm. The latter effect is however delayed and weak in the Tg8 strain. Therefore, MAOA-deficiency has only slightly altered the noradrenergic regulations of the respiratory network. 相似文献
24.
25.
目的 :研究树 鼠句脑缺血时单胺氧化酶 (MAO)活化在脑缺血时心功能障碍以及扩布性抑制中的可能作用。方法 :采用光化学法诱导树 鼠句血栓性脑缺血 ,测定缺血区及血清MAO活性、多巴胺及去甲肾上腺素 (NA)水平 ,经电镜观察脑及肾上腺的超微结构。记录仪检测心率(HR)、左室收缩压峰值 (LVSP) ,左室瞬间收缩与舒张最大速率 (±dp/dtmax) ,左室舒张末期压力 (LVEDP) ,平均动脉压 (MAP)。结果 :树鼠句脑缺血过程中血清NA先升高 (由 11.60± 0 .73ng/ml升高至18.46± 0 .3 9ng/ml,P <0 .0 1) ,72h后降至 8.3 2± 1.86ng/ml;血清MAO活性逐渐升高 ,达 2 10 .1± 2 6.67U/ml(P <0 .0 1) ,72h降低至对照水平 ;心功能指标 (±dp/dtmax,LVSP ) ,尤其是HR明显降低 ,由3 17.0± 98.0 1beat/min降至 2 3 7.4± 3 1.90beat/min(P <0 .0 1) ,于2 4h恢复至对照水平。结论 :血栓性脑缺血时血清NA水平明显取决于MAO活性的变化 ,后者对脑缺血时心脏舒缩功能可能具有调节作用。 相似文献
26.
C. Strazielle P. Krémarik J.-F. Ghersi-Egea R. Lalonde 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1998,121(1):35-45
Lurcher mutant mice are characterized by massive degeneration of cerebellar Purkinje cells and granule cells and by deficits in motor
coordination. Regional brain variations of cytochrome oxidase (CO) activity were analyzed to identify those brain regions
with abnormal metabolic activity as a secondary consequence of the cerebellar atrophy and to establish the relationship between
CO activity and motor deficits. Lurcher mutants had higher CO activity in all three cerebellar deep nuclei than normal littermate controls of the same background
strain. Higher CO activity was also found in Lurcher mutants in brain regions directly connected to the cerebellum, such as the lateral vestibular nucleus, the cochlear nucleus,
the red nucleus, the ventrolateral thalamus, the dorsal raphe, the interpeduncular nucleus, and the inferior colliculus. By
contrast, there was a sharp decrease in CO activity in the inferior olive. As for brain regions not directly connected to
the cerebellum, higher CO activity was observed in the trigeminal motor nucleus and the CA1 molecular layer of the hippocampus,
which highlights probable transsynaptic alterations as a secondary consequence of cerebellar atrophy. A positive correlation
between CO activity in the red nucleus and latencies before falling in two motor-coordination tests indicates that a compensatory
increase of metabolic activity in a cerebellar efferent region is associated with improved behavior.
Received: 15 September 1997 / Accepted: 3 March 1998 相似文献
27.
Ken Dewitte Marc Claeys Emeline Van Craenenbroeck Koen Monsieurs Hein Heidbuchel Vicky Hoymans Tibor Stoop 《Pathophysiology》2019,26(1):53-59
Aims
We explored the effect of remote ischaemic conditioning (RIC) on endothelial function and on circulating mediators.Methods and results
In 20 healthy male volunteers (mean age 31?±?10 years), flow-mediated dilation (FMD) was measured before and after 20?min of arm ischaemia, followed by reperfusion. Remote ischaemic conditioning (RIC) was performed by applying 3 cycles of 5?min of ischaemia of the leg at the onset of index arm ischaemia. Each volunteer underwent the IR-induced vascular injury protocol with and without RIC in a crossover study design.In the control group, IR significantly reduced FMD (5.9?±?2.9% before IR vs. 2.2?±?3.7% after IR; p?<?0.001). This effect was significantly attenuated by performing RIC (FMD of 5.5?±?3.1% before IR vs. 4.0?±?3.4% % after IR; p for interaction?=?0.01). Serum levels of SOD and ADMA increased significantly whereas MCP-1 and VEGF levels decreased significantly.Only changes in SOD levels were significantly related to the degree of RIC induced protection (r²?=?0.34; p?=?0.018).Conclusion
RIC has protective effects against endothelial IR injury. Our biomarker study suggests that anti-oxidative stress mediators, such as SOD, seem to be more involved in the pathogenesis of RIC-induced protection in humans than angiogenesis factors or chemo-attractant cytokines. 相似文献28.
El Benna J Hayem G Dang PM Fay M Chollet-Martin S Elbim C Meyer O Gougerot-Pocidalo MA 《Inflammation》2002,26(6):273-278
Superoxide anion (O2°-)production by neutrophil NADPH oxidase participates in arthritic joint lesion formation. Proinflammatory cytokines such as tumor necrosis factor (TNF), interleukin 8 (IL-8) and granulocyte/macrophage-colony stimulating factor (GM-CSF) have a priming effect on neutrophil NADPH oxidase activity. NADPH oxidase activation is dependent on phosphorylation of p47phox, a cytosolic component of the enzyme. We studied O2°-production and p47phox phosphorylation in synovial fluid (SF) from patients with rheumatoid arthritis (RA) and spondylarthropathy (SpA) according to TNF, IL-8 and GM-CSF levels. O2°-production by neutrophils isolated from SF of all the arthritis patients (RA and SpA) was higher than that of circulating resting neutrophils and when stimulated with fMLP or PMA. In addition, p47phox was partially phosphorylated in SF neutrophils compared to circulating neutrophils. High levels of TNF and IL-8 (but not GM-CSF) are detected in patient's SF (compared to circulating blood levels). TNF levels were significantly higher in RA than in SpA SF. These results suggest that increased NADPH oxidase activity could be involved in arthritic joint inflammation through increased p47phox phosphorylation. This could be the result of the presence of high levels of priming agents such as TNF and IL-8 but not GM-CSF. 相似文献
29.
Yasushi Kondoh Matsutaro Murakami Weimin Yin Shigenori Mizusawa Hiroyuki Nakamichi Ken Nagata 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1994,99(3):375-382
The distribution of functionally active monoamine oxidase type A (MAO-A) was investigated by in vivo quantitative autoradiography using [14C]clorgyline in normal, conscious rat brain. [14C]clorgyline was synthesized by the methylation reaction of N-desmethylclorgyline using [14C]methyliodide. Sixty minutes after [14C]clorgyline administration (1.58 MBq/animal i.v.), the brains were removed and prepared for autoradiography by washing the brain sections with 5% trichloroacetic acid solution to remove the nonbinding free tracer. The amount of MAO-A was calculated from the regional acid-insoluble tissue radioactivity and the specific activity of the tracer. The highest amount of MAO-A (5.84 nmol/g tissue) was found in the locus coeruleus. The interpeduncular nucleus, habenular nucleus, fasciculus retroflexus, and solitary tract nucleus possessed over 1.6 nmol/g tissue of MAO-A. Among 23 regions of interest, the lowest amount of MAO-A (0.37 nmol/g tissue) was found in the globus pallidus. The findings of this study suggest that the pattern of MAO-A parallels both in neuroanatomical distribution and in density that of norepinephrine and serotonin innervation. The MAO-A concentration was, however, relatively low in the dopamine-related areas. This corresponded to the previous results obtained by histochemical analysis. In addition, among the white matter structures, a high amount of MAO-A was found specifically in the fasciculus retroflexus. 相似文献
30.
A negative relationship between platelet monoamine oxidase (MAO) activity and Sensation Seeking (SS) has been reported in several studies. This study evaluates the possible contribution of autonomic nervous system (ANS) activity to this relationship. Additionally, confirmatory factor analysis was used to create models of ANS concepts from a larger number of psychophysiological variables. Skin conductance (SC) and heart rate (HR) were recorded from 46 men and 49 women during a two-session protocol that included rest periods, a balloon stress, a series of tones, and two tasks: two-flash threshold and tachistoscopic recognition. Results showed that the best-fitting models for both rest and task periods included concepts of SC base levels (“arousal”), SC lability, and HR, and were quite similar for men and women. MAO activity correlated positively with SC concepts, most strongly for women. Women showed negative relationships between sensation seeking and both SC arousal and HR concepts. In contrast, men showed evidence of positive relationships between SC concepts and an active life style. The sex differences and response specificity in these relationships make it unlikely that ANS activity mediates the negative MAO-SS relationship. 相似文献