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81.
Emilio Abecia Begoña Martínez-Jarreta Yolanda Casalod Blanca Bell Isabel Pinilla Francisco M. Honrubia 《International ophthalmology》1996,20(1-3):79-82
Purpose: To investigate possible associations between genetic markers and Primary Open-Angle Glaucoma (POAG). Methods: A number of genetic markers were typed in 84 unrelated patients with POAG and compared with a random sample of healthy individuals. The markers were Transferrin, Group Specific Component, G1m (1), G1m (2) and G3m (5) Allotypes, Adenylate Kinase, Adenosin Deaminase, Glyoxalase I and Acid Phosphatase and PCR-based markers HLA-DQA1 and D1S80. Results: No significant differences were found except the strong association between the group of POAG patients and Acid Phosphatase ACP*C allele (2 = 32.86; p < 0.0001). Conclusions: Since Acid Phosphatase gene is localized to chromosome 2p23, this result could be a first comprehensive step in the localization of POAG genes. 相似文献
82.
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
83.
María Cristina Camilión de Hurtado María Isabel Argel Horacio Eugenio Cingolani 《Naunyn-Schmiedeberg's archives of pharmacology》1981,317(3):219-224
Summary The influence of respiratory and metabolic acid-base alterations on the myocardial sensitivity to catecholamines was studied in the isolated rat atria. The ability of noradrenaline for increasing the atrial rate was enhanced during alkalosis and conversely, it was decreased by acidosis. These changes in sensitivity shifted the concentration-effect curve for noradrenaline to the right by about 0.5 log unit when the pH was lowered from 7.60 to 7.00. No changes in the maximum attainable response were detected. Essentially the same shifts of the concentration-effect curves were obtained with changes in pH brought about by altering the pCO2 or at constant pCO2. The decrease in the pH produced a similar shift to the right of the concentration-effect curve for isoprenaline, after the extraneuronal uptake inhibition by hydrocortisone and also in atria tissue with low content of endogenous noradrenaline (reserpine-pretreated and newborn rats). The ability of isoprenaline for increasing cyclic AMP levels in atrial tissue was also enhanced by alkalosis and decreased by acidosis. However, the shift to the right of the concentration-effect curve for cyclic AMP induced by the decrease in the pH was greater than the shift detected in the chronotropic-effect curve. In addition a decrease in the maximum increment of cyclic AMP was detected under acidosis, in spite of equal maximal chronotropic response.Our results support the hypothesis that the alterations in the sensitivity to catecholamines induced by the changes in pH are not due to a release of endogenous noradrenaline nor to alterations of the mechanisms which remove catecholamines from the biophase. The fact that cyclic AMP response to catecholamines was also reduced by acidosis strongly suggests that the mechanism(s) involved is located in the earlier steps of the events leading to the chronotropic effect of the -agonists. 相似文献
84.
Alcohol and Sober Mood State in Female Social Drinkers 总被引:1,自引:0,他引:1
Isabel M. Bimbaum PhD Thomas H. Taylor PhD Elizabeth S. Parker PhD 《Alcoholism, clinical and experimental research》1983,7(4):362-368
The goals of the present study were to measure the relationship between alcohol consumption in 93 female social drinkers and their cognitive functioning and mood in the sober state, and to investigate the possible causal effects of alcohol consumption on these variables. In the first test session, a limited relationship was seen between previous alcohol consumption and sober cognitive performance. A strong relationship was found between alcohol consumption and self-reported depression and anger in the sober state. Either a prolonged reduction in alcohol consumption or a prolonged maintenance of alcohol consumption was undertaken by random subsets of the original sample. In the second test session 6 weeks later, women who had been randomly selected to reduce their alcohol intake showed decreases in depression, anger, and mental confusion when they were sober, relative to women who maintained or increased their alcohol consumption over the same period of time. We found no changes in cognitive performance in these groups. We concluded that the simplest explanation of the findings is that relatively low levels of alcohol consumption produce substantial increases in depression and anger in the sober state in female social drinkers. The value of considering alcohol consumption as a continuous variable rather than a dichotomous variable with "safe" and "unsafe" zones was discussed. 相似文献
85.
Acidic Amino Acids and Self-stimulation of the Prefrontal Cortex in the Rat: A Pharmacological Study
The effects of intraventricular and intracortical microinjections of acidic amino acid antagonists on self-stimulation (SS) of the medial prefrontal cortex (MPC) were investigated. Self-stimulation was measured by depressing a lever in a standard chamber. Spontaneous motor activity of the animal and SS of the contralateral non-injected MPC were used as control for non-specific effects of the drugs. Intraventricular microinjections of gamma-d-glutamylglycine (DGG), an antagonist of NMDA, kainate and quisqualate receptors, or 2-amino-5-phosphonovalerate (AP-5), a specific antagonist of NMDA receptors, produced a dose-related decrease of SS in the MPC. Spontaneous motor activity of the animal was not significantly affected. Unilateral microinjections into the medial prefrontal cortex of DGG or AP-5 produced a decrease of SS in the ipsilateral side while no effects were found on the contralateral MPC. On the contrary, intraventricular microinjections of gamma-d-glutamyltaurine (Glu-tau), an antagonist with more relative affinity for kainate and quisqualate receptors, produced a dose-related decrease of both self-stimulation and spontaneous motor activity of the rats. Moreover, intracortical microinjections of Glu-tau had no effect on self-stimulation of this cortical area. These results suggest that acidic amino acids through NMDA, but not kainate or quisqualate, receptors could be part of the neurochemical substrate underlying SS of the MPC in the rat. 相似文献
86.
87.
88.
Olivia Fletcher Lorna Gibson Nichola Johnson Dan R Altmann Jeffrey M P Holly Alan Ashworth Julian Peto Isabel Dos Santos Silva 《Cancer epidemiology, biomarkers & prevention》2005,14(1):2-19
We reviewed all English-language articles on associations among circulating levels of the insulin-like growth factors (IGF) and their binding proteins (IGFBP), polymorphisms in their genes, and breast cancer risk. In premenopausal women, five of eight IGF-I studies and four of six IGFBP-3 studies of circulating levels found that women in the highest quantile had more than twice the risk of developing breast cancer of those in the lowest, although in some this effect was only apparent at young ages. In postmenopausal women, however, there was no consistent effect. A simple sequence length polymorphism 1 kb 5' to IGF-I was examined in relation to circulating levels of IGF-I (12 studies) or breast cancer risk (4 studies), but there was no convincing evidence of any effect. For an A/C polymorphism 5' to IGFBP-3, all three studies were consistent with a modest effect on circulating levels, but no evidence of a direct effect on breast cancer risk was seen in the only relevant study. Variation within the reference range of IGF-I and IGFBP-3 may confer only modest increases in breast cancer risk, and any single polymorphism may only account for a small proportion of that variation. Nevertheless, population attributable fractions for high circulating levels of IGF-I and IGFBP-3 and for common genetic variants could be substantial. Further large studies, or combined analysis of data from existing studies, are needed to quantify these effects more precisely. 相似文献
89.
Isabel Monteiro-Grillo Pedro Marques-Vidal Marília Jorge 《Clinical & translational oncology》2005,7(11):499-503
Purpose To compare the quality-of-life (QoL) and psycho-social changes in a group of patients with early breast cancer who underwent
conservative surgery (BCS) or modified radical mastectomy (MRM).
Methods Self-administered questionnaire assessing body image perception, social habits, sexual attraction and self-consciousness with
relatives/friends, was randomly assigned to 125 patients (61 BCS, 64 MRM; aged 53±8 and 50±9 years, respectively, p=NS).
Results MRM patients reported a significantly higher frequency of changes in body image perception and other related social behaviour
such as avoiding going to the beach or using low-cut clothes, and reticence with friends. Conversely, no differences were
found regarding sexuality, denial of the disease by the husband/partner, or concealing the disease from family members. Also,
no significant differences were found between patients above and below the age of 50 years, for all variables studied after
adjustment for surgical procedure.
Conclusions Modified radical mastectomy has a negative effect on body image perception and in social behaviour patterns of patients and
with a concomitant decrease in QoL. The sexuality of the patient is not significantly affected. 相似文献
90.
The diagnostic usefulness of sentinel lymph node biopsy (SLNB) has been well established, but its therapeutic value remains
unproven. First introduced by Morton and colleagues, the SLNB procedure is now widely available, and markedly enhances our
ability to pathologically stage the regional nodes.
Although the SLN status is acknowledged as the most powerful indicator of prognosis in melanoma, there is no evidence to-date,
of survival advantage for complete lymphadenectomy in SLN-positive patients. Also, there is no effective adjuvant therapy
that could benefit these sentinel node-positive patients, as yet. Additionally, new data have emerged indicating a possible
increase in local/in-transit recurrence following complete lymphadenectomy in sentinel node-positive patients. To understand
fully and to evaluate these observations we need information from randomized controlled trials.
Major changes have occurred following the latest revision of melanoma staging system (AJCC, 6th edition). Concerning N category,
these include the incorporation of the number of metastatic lymph nodes, the tumour burden of nodal metastases, and the ulceration
of the primary tumour. The data obtained from the new staging system will reflect differences in prognosis that were not previously
emphasized and which, we hope, will serve as a guide to more accurate analysis of metastatic pathways in cutaneous melanoma
as well as a rationale for new forms of treatment. 相似文献