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91.
Interaction of family history of breast cancer and dietary antioxidants with breast cancer risk (New York,United States) 总被引:1,自引:0,他引:1
Christine B. Ambrosone James R. Marshall John E. Vena Rosemary Laughlin Saxon Graham Takuma Nemoto Jo L. Freudenheim 《Cancer causes & control : CCC》1995,6(5):407-415
We sought to determine if specific dietary antioxidants may be particularly effective in reducing breast cancer risk for women reporting family history (FH) of breast cancer in a first-degree relative. Interviews regarding usual diet, health, and family histories were conducted with 262 premenopausal and 371 postmenopausal women with incident, primary breast cancer from western New York (United States). These women were frequencymatched by age and county of residence with community controls. Among premenopausal women, there was a significant interaction between FH and -tocopherol; -tocopherol was associated with significantly decreased risk among FH+ women (adjusted fourth-quartile odds ratio [OR]=0.01, 95 percent confidence interval [CI]=0.0–0.3). This association was much weaker for FH-women [OR=0.7, CI=0.4–1.2]. For FH-women, a significant inverse association was observed between -carotene and premenopausal breast-cancer risk (OR=0.4, CI=0.3–0.5), but not for FH+ women (OR=0.5, CI=0.1–4.0). Similar relationships, although not as strong, were noted among postmenopausal women. Although limited by small numbers, these results suggest that biologic mechanisms of tumorigenesis may differ in FH+ and FH-women, and that -tocopherol may be a potential chemopreventive agent for women with a family history of breast cancer, particularly premenopausal women.This research was conducted by the Department of Social and preventive Medicine, State University of New York at Buffalo. This publication is supported in part by grants CA11535 and 5 R25 CA1820117 from the US National Cancer Institute and PDT-434 from the American Cancer Society. Dr Freudenheim is a recipient of a Research Career Development Award from the National Cancer Institute (CA01633). This work is solely the responsibility of the authors and does not necessarily represent the views of the NCI. 相似文献
92.
Summary The effects of centrally administered atrial natriuretic peptide (ANP) on the brain water and electrolyte contents were investigated in a rodent subarachnoid haemorrhage (SAH) model. SAH caused statistically significant increases in the brain sodium and water contents, while the potassium content did not change significantly, indicating that the brain oedema could be classified as having a primarily vasogenic component. Two g or 5 g of rat ANP administered into the lateral ventricle at the time of SAH induction statistically significantly decreased the water and sodium accumulation measured 90 minutes following SAH. The same treatment did not inhibit development of brain oedema measured 3 hours following SAH. However, when 5 g of ANP was administered intraventricularly at the time of SAH induction and also 90 minutes later, the brain oedema 3 hours following SAH was again reduced statistically significantly. These effects of ANP were found not to be mediated by primary changes in serum osmolality and electrolyte concentrations.The present results confirm that centrally administered ANP may act directly on the central nervous system to inhibit brain water and sodium accumulation in SAH-induced brain oedema. The potentials of influencing the central neuro-endocrine system as a novel way of the treatment of brain oedema are discussed.Supported by Grant OTKA I/3 2728 and ETT T110/ 1990. 相似文献
93.
Fátima Martel M. João Martins Isabel Azevedo 《Naunyn-Schmiedeberg's archives of pharmacology》1996,354(3):305-311
1-Methyl-4-phenylpyridinium (MPP+), the neurotoxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), is efficiently taken up and accumulated by rat hepatocytes. However, the nature of the mechanism(s) involved in the hepatic uptake of MPP+ remains partially unknown. The aim of the present study was to further characterize the hepatic uptake of 3H-MPP+, namely by investigating the interactions of catecholamines (which are also efficiently taken up by rat hepatocytes) with MPP1 transport.The accumulation of 3H-MPP+ in isolated rat hepatocytes occurred through saturable and non-saturable mechanisms. The kinetics of the saturable component of 3H-MPP+ uptake was as follows: Vmax = 181.3 ± 11.1 pmol mg protein–1 min–1 and Km = 47.1 M (27.9, 66.3) (n = 5). The diffusion constant (in ml mg protein–1 min–1) for the non-saturable uptake of 3H-MPP+ was 0.00068 (0.00052, 0.00083) (n = 5). From the analysis of the time course of 3H-MPP+ accumulation at a substrate concentration of 100 nM 3H-MPP+, it was found that the rate constant of inward transport of 3H-MPP+ into hepatocytes (kin) was 15.7 ± 3.8 l mg protein–1 min–1, the rate constant of outward transport of 3H-MPP+ from hepatocytes (kout) was 0.077 ± 0.023 min–1 and the equilibrium accumulation (Amax) of 3H-MPP+ was 20.2 ± 2.0 pmol mg protein–1 (n = 36). Decynium22 (1,1-diethyl-2,2-cyanide; 1 M) significantly reduced kin to 6.1 ± 1.8 l mg protein–1 min–1 (P < 0.05) and the equilibrium accumulation (Amax) of 3H-MPP+ to 9.6 ± 1.3 pmol mg protein–1 (P < 0.005) (n = 36). 3H-MPP+ accumulation (in cells incubated with 200 nM 3H-MPP+) was sensitive to (–)-adrenaline, (–)-isoprenaline, (–)-dopamine, (±)-adrenaline and (–)-noradrenaline. The most potent catecholamine in inhibiting 3H-MPP+ uptake was (–)-adrenaline, with an IC50 of 99 (22, 449) M (n = 6). (–)-Adrenaline competitively inhibited 3H-MPP+ uptake, as it significantly increased the Km value of 3H-MPP+ uptake (to 125.4 M (63.6; 187.1); P < 0.02; n = 3) but did not change the Vmax value. The cyanide-derivatives decynium22 and cyanine863 (1-ethyl-2-([1,4-dimethyl-2-phenyl-6-pyrimidinylidene]methyl)quinolinium), which inhibit uptake2 as well as the apical type of the renal transporter for organic cations, potently inhibited 3H-MPP+ uptake with IC50's of 1.4 (0.4–5.3) (n = 6) and 6.5 (2.6–16) (n = 4) M, respectively. Under conditions of monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT) inhibition with either pargyline (500 M + Ro01-2812) (3,5-dinitropyrocatechol; 2 M) or pargyline (500 M) + U-0521(3,4-dihidroxy-2-methyl-propiophenone; l2 M)), (–)-adrenaline (up to 1 mM) had no inhibitory effect on the uptake of 3H-MPP+. Moreover, the uptake of 3H-MPP+ in the presence of pargyline + Ro 01-2812 was significantly lower (66.9 ± 30.4%; P < 0.05; n = 4) than in the absence of these compounds. Therefore, the effect of these MAO and COMT inhibitors on 3H-MPP+ uptake was examined. Interestingly enough, pargyline, Ro 01-2812 and U-0521 were found to inhibit the uptake of 3H-MPP+ (in cells incubated with 200 nM 3H-MPP+): 500 M pargyline, 2 M Ro 012812 and 100 M U-0521 decreased the accumulation of 3H-MPP+ to 38.1 ± 6.8 (n = 5), 60.5 ± 10.1(n = 7) and 71.3 ± 14.5 (n = 7) % of control, respectively.It is concluded that 3H-MPP+ is efficiently taken up by rat hepatocytes by a carrier-mediated mechanism sensitive to catecholamines, decynium22 and cy anine863, and to the enzyme inhibitors pargyline, Ro 01-2812 and U-0521. 相似文献
94.
95.
Several sexual counseling and education programs exist for the disabled population. Some of these focus upon staff awareness and desentization about sexuality, while others are specifically designed to provide sexual information and counseling for disabled individuals. These programs represent significant advances in the area of sexuality and disabiltiy. However, reliance upon outcome variables like much improved or no change has moderated the accurate evaluation of such approaches. This paper describes a group treatment program for sexual behavior and attitude change in spinal cord injured couples. Also, preliminary data from objective outcome measures relevant to this intervention is presented.This study was supported in part by Grant No. 16-P-56818-0 from the Rehabilitation Services Administration, Department of HEW, Washington, D.C. 相似文献
96.
97.
João Luis Callegari Lopes Izabel Cristina Casanova Myrian C. Garcia de Figueireido Francisco Carlos Nather Wagner E. Paiva Avelar 《Archives of environmental contamination and toxicology》1992,23(3):351-354
The mussel Anodontites trapesialis (Lam, 1819) was used as an indicator of organochlorine pollutants in the Pardo River, located in the municipality of Ribeirão Preto (21° 07S and 47° 45W), State of São Paulo, Brazil.Biological monitoring was performed for one year at the site of a sugar cane grove on the left bank of the river. Forty-three animals were placed in two aluminum enclosures on the river bottom at this site and 4 animals of each enclosure were sacrificed for pesticide analysis at 3-month intervals, each collection corresponding to one season of the year.The animals were found to have been exposed to DDT, lindane, heptachlor, aldrin and dieldrin. Endrin was not detected in any of the analyses.Research supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP). 相似文献
98.
Delumeau JC Tencé M Marin P Cordier J Glowinski J Prémont J 《The European journal of neuroscience》1991,3(6):539-550
Adenosine has a broad array of actions on neurons but astrocytes also possess adenosine receptors. We have previously shown that adenosine, by acting on astrocytes in the striatum, can modulate neuronal responses mediated by receptors coupled to phospholipase C through an astrocyto - neuronal interaction. In addition, adenosine was found to potentiate the alpha1-adrenergic production of inositol phosphates in astrocytes. The mechanism involved in this potentiation was further investigated by examining the effects of adenosine and alpha1-adrenergic receptor agonists on cytosolic Ca2+ in cultured striatal astrocytes from the embryonic mouse in primary culture. When used alone, methoxamine, a selective agonist of alpha-adrenergic receptors or 2-chloroadenosine, a stable analogue of adenosine, induced a transitory increase in cytosolic Ca2+, but their combined addition led to a sustained increase in cytosolic Ca2+, which seems to be due to a Ca2+ influx, because it was not observed in the absence of external Ca2+. Voltage independent Ca2+ channels contribute to this process and different blockers of voltage-operated calcium channels, such as dihydropyridines, phenylalkylamines, La3+ or Co2+ were ineffective in suppressing the sustained cytosolic Ca2+ elevation. Three observations suggest the implication of arachidonic acid in the observed potentiation: (i) arachidonic acid induced a sustained elevation of cytosolic Ca2+ similar to that evoked by the coapplication of methoxamine and 2-chloroadenosine; (ii) the addition of arachidonic acid during the calcic plateau produced by the combined application of the agonists did not increase further cytosolic Ca2+ levels; (iii) in the presence of methoxamine, 2-chloroadenosine induced a release of arachidonic acid. The stimulation of phospholipase C and the resulting activation of protein kinase C induced by methoxamine seem to be required for the potentiating effect of 2-chloroadenosine on cytosolic Ca2+. In fact, the direct activation of protein kinase C by an exogenous diacylglycerol analogue mimicked the effect of methoxamine because, in this condition, 2-chloroadenosine alone evoked a sustained elevation of cytosolic Ca2+. Therefore, methoxamine, through the successive activation of phospholipase C and protein kinase C, could allow a lipase, probably phospholipase A2, to be stimulated by 2-chloroadenosine. Arachidonic acid has already been shown to trigger the opening of K+ channels and the formation of inositol phosphates in other cell types. Therefore, in striatal astrocytes, 2-chloroadenosine, through an arachidonic acid-mediated hyperpolarization, could increase the Ca2+ driving force and thus improve Ca2+ influx through inositol phosphate-gated channels. This hypothesis is further supported by the suppressing effect of a 50 mM KCI-induced depolarization on the long lasting elevation of cytosolic Ca2+ seen in the combined presence of 2-chloroadenosine and methoxamine. 相似文献
99.
Yves Claustre Danielle De Peretti Philippe Brun Christiane Gueudet Nathalie Allouard Richard Alonso Jo?lle Lourdelet André Oblin Gabrielle Damoiseau Dominique Fran?on Marie-Fran?oise Suaud-Chagny Régis Steinberg Mireille Sevrin Hans Schoemaker Pascal George Philippe Soubrié Bernard Scatton 《Neuropsychopharmacology》2003,28(12):2064-2076
SSR181507 ((3-exo)-8-benzoyl-N-[[(2S)7-chloro-2,3-dihydro-1,4-benzodioxin-1-yl]methyl]-8-azabicyclo[3.2.1]octane-3-methanamine monohydrochloride) is a novel tropanemethanamine benzodioxane derivative that possesses high and selective affinities for D2-like and 5-HT(1A) receptors (K(I)=0.8, 0.2, and 0.2 nM for human D(2), D(3), and 5-HT(1A), respectively). In vivo, SSR181507 inhibited [(3)H]raclopride binding to D(2) receptors in the rat (ID(50)=0.9 and 1 mg/kg, i.p. in limbic system and striatum, respectively). It displayed D(2) antagonist and 5-HT(1A) agonist properties in the same concentration range in vitro (IC(50)=5.3 nM and EC(50)=2.3 nM, respectively, in the GTPgammaS model) and in the same dose range in vivo (ED(50)=1.6 and 0.7 mg/kg, i.p. on striatal DA and 5-HT synthesis, respectively, and 0.03-0.3 mg/kg, i.v. on dorsal raphe nucleus firing rate). It selectively enhanced Fos immunoreactivity in mesocorticolimbic areas as compared to the striatum. This regional selectivity was confirmed in electrophysiological studies where SSR181507, given acutely (0.1-3 mg/kg, i.p.) or chronically (3 mg/kg, i.p., o.d., 22 days), increased or decreased, respectively, the number of spontaneous active DA cells in the ventral tegmental area, but not in the substantia nigra. Moreover, SSR181507 increased both basal and phasic DA efflux (as assessed by microdialysis and electrochemistry) in the medial prefrontal cortex and nucleus accumbens, but not in the striatum. This study shows that the combination of D(2) receptor antagonism and 5-HT(1A) agonism, in the same dose range, confers on SSR181507 a unique neurochemical and electrophysiological profile and suggests the potential of this compound for the treatment of the main dimensions of schizophrenia. 相似文献
100.
Luiz A Benvenuti Francisco O S Fran?a Kátia C Barbaro José R Nunes Jo?o L C Cardoso 《Toxicon》2003,42(3):331-334
A 36-year old woman was bitten on the left ankle by a Bothrops jararacussu, and died 45 min after the bite. At necropsy, there were local signs of envenoming with haemorrhage, thrombosis and necrosis of the subcutaneous and muscular tissue. Multiple fibrin and platelet thrombi were found in the microcirculation of the heart and lungs, suggesting the occurrence of disseminated intravascular coagulation. Pulmonary haemorrhage probably secondary to the action of haemorrhagins, consumption coagulopathy and disseminated intravascular coagulation was the immediate cause of death. Intravenous inoculation of the venom could have occurred in the present case, which would explain the rapid onset of coagulation disorders, haemorrhage and death. 相似文献