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921.
922.
Hu Y McIntosh GH Le Leu RK Upton JM Woodman RJ Young GP 《The British journal of nutrition》2011,106(4):572-582
Certain forms of dietary Se may have advantages for improving human Se status and regulating the risk for disease, such as cancers, including colorectal cancer (CRC). The present study compared the effects of a Se-enriched milk protein (dairy-Se) with a Se-rich yeast (yeast-Se) on plasma Se levels and rectal selenoprotein gene expression since we reasoned that if these genes were not regulated, there was little potential for regulating the risk for CRC in this organ. A total of twenty-three healthy volunteers with plasma Se in the lower half of the population range were supplemented with dairy-Se (150 μg/d) or yeast-Se (150 μg/d) for 6 weeks, followed by 6 weeks of washout period. Blood was sampled every 2 weeks, and rectal biopsies were obtained before and after Se supplementation and after the washout period. Plasma Se levels and glutathione peroxidase (GPx) activity, and rectal mRNA of selenoprotein P (SeP), cytosolic GPx-1 (GPx-1), gastrointestinal GPx-2 (GPx-2) and thioredoxin reductase-1 (TrxR-1) were measured. Plasma Se levels increased rapidly in both Se groups (P < 0·001); plasma GPx activity was not significantly changed. Rectal SeP mRNA increased at 6 weeks compared with baseline in both Se groups (P < 0·05); only dairy-Se resulted in a sustained elevation of SeP after the washout period (P < 0·05). Rectal GPx-1 and GPx-2 mRNA were higher with dairy-Se (P < 0·05) than with yeast-Se at 6 weeks. In conclusion, three rectal selenoprotein mRNA were differentially regulated by dairy-Se and yeast-Se. Changes in rectal selenoproteins are not predicted by changes in plasma Se; dairy-Se effectively regulates the expression of several rectal selenoproteins of relevance to the risk for CRC. 相似文献
923.
Duggan ME Duong LT Fisher JE Hamill TG Hoffman WF Huff JR Ihle NC Leu CT Nagy RM Perkins JJ Rodan SB Wesolowski G Whitman DB Zartman AE Rodan GA Hartman GD 《Journal of medicinal chemistry》2000,43(20):3736-3745
Modification of the potent fibrinogen receptor (alpha(IIb)beta(3)) antagonist 1 generated compounds with high affinity for the vitronectin receptor alpha(v)beta(3). Sequential modification of the basic N-terminus of 1 led to the identification of the 5,6,7, 8-tetrahydro[1,8]naphthyridine moiety (THN) as a lipophilic, moderately basic N-terminus that provides molecules with excellent potency and selectivity for the integrin receptor alpha(v)beta(3). The THN-containing analogue 5 is a potent inhibitor of bone resorption in vitro and in vivo. In addition, the identification of a novel, nonpeptide radioligand with high affinity to alpha(v)beta(3) is also reported. 相似文献
924.
925.
Several groups are developing ultra-miniature x-ray machines for clinical use in radiation therapy. Current systems are for interstitial radiosurgery and for intravascular insertion for irradiation to prevent re-stenosis. Typical generating voltages are low, in the 20 to 40 kV range. It is well established that the biological effectiveness of such low-energy photons is large compared with higher-energy gamma rays, because of the dominance of photoelectric absorption at low energies. We have used microdosimetric analyses to estimate RBEs for such devices, both at low doses and clinically relevant doses, relative to radiations from 60Co, 192Ir, 125I and 90Sr/90Y. The RBEs at clinically relevant doses and dose rates for these low-energy x-ray sources are considerably above unity, both relative to 60Co and to 192Ir photons, and also relative to 125I and 90Sr/90Y brachytherapy sources. As a function of depth, the overall effect of the change in dose and the change in beam spectrum results in beams whose biologically weighted dose (dose x RBE) decreases with depth somewhat more slowly than does the physical dose. The estimated clinically relevant RBEs are sufficiently large that they should be taken into account during the treatment design stage. 相似文献
926.
The clinical outcome for methamphetamine (MAP) abusers is variable. MAP exerts its biological activity through rapid conversion to amphetamine (AP) and MAP itself. The dopamine transporter (DAT) is the main modulator of MAP/AP-induced dopamine release and dopamine neurotoxicity, and is also the major regulator of dopamine level in the brain. We tested for an association between a DAT-gene polymorphism and clinical variations in MAP abusers. A total of 146 MAP abusers were enrolled in the study and classified into three clinically distinct groups: MAP dependence (n = 30), MAP psychosis (n = 88) and chronic MAP psychosis (n = 28). Patients with schizophrenia (n = 79) and healthy controls (n = 72) were also recruited for the study. The 40 base pair variable number tandem repeat polymorphism in the 3'-untranslated region of the DAT was the focus of the investigation. The subjects were all Chinese residents of Taiwan. The respective allelic frequencies for DAT repeats 11, 10 and 9 were 0.067, 0.833 and 0.083 for the MAP-dependence group, 0.006, 0.864 and 0.119 for the MAP psychosis group, 0.018, 0.893 and 0.089 for the chronic MAP psychosis group, 0.019, 0.911 and 0.07 for the schizophrenic controls, and 0.021, 0.889 and 0.083 for the healthy controls. No significant associations were demonstrated between this DAT polymorphism in genotype and allele frequency and the clinical outcome of MAP abusers. The biological relevance of the variable number tandem repeat polymorphism in the 3'-untranslated region of DAT in MAP abusers was not demonstrated in this study. 相似文献
927.
Resident and oil-elicited inflammatory peritoneal macrophages (PM phi) from competent C3HeB/FeJ and genetically deficient C3H/HeJ mice were characterized for their Fc receptor (FcR)-dependent binding, phagocytic and ADCC functions during in vitro differentiation under the influence of mouse recombinant interferon-gamma (rIFN-gamma), interferon-alpha/beta (IFN-alpha/beta) fetal bovine serum (FBS), or in serum-free medium. Freshly cultured resident PM phi from C3HeB/FeJ mice had low levels of FcR-mediated phagocytosis in response to mouse monoclonal IgG gamma 2a, IgG gamma 2b or IgG gamma 1, opsonized sheep erythrocytes as compared to oil-elicited inflammatory PM phi from the same strain. Resident PM phi were uniformly upregulated in their FcR-dependent phagocytosis after 24-48 h in vitro culture with FBS to levels approximating that of freshly cultured inflammatory PM phi which were also further upregulated after 24 h in vitro culture with FBS. Both resident and inflammatory PM phi were upregulated largely by an autostimulatory process in that they increased their FcR-mediated phagocytosis in serum-free RPMI-1640 medium without the addition of rIFN-gamma or IFN-alpha/beta, although FBS further augmented FcR upregulation. A synergistic effect of FBS and rIFN-gamma was required for total reconstitution of FcR-mediated phagocytosis of FcR-incompetent C3H/HeJ inflammatory PM phi in that FBS or rIFN-gamma alone only partially reconstituted FcR function, whereas in combination full reconstitution occurred. Thus, macrophages from competent C3HeB/FeJ mice were upregulated in their FcR-mediated functions largely by an autostimulatory process, presumably dependent on endogenous of IFN-beta, whereas, genetically-deficient C3H/HeJ macrophages required exogenous rIFN-gamma in combination with fetal bovine serum for synergistic reconstitution of FcR functions. The uniform upregulation of FcR-dependent effector functions in vitro appears to provide an efficient system for enhanced immune function during differentiation which may be applicable to in vivo situations. 相似文献
928.