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61.
62.
A preliminary, clinical pharmacological assessment of L-659,066, a novel alpha 2-adrenoceptor antagonist.
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![点击此处可从《British journal of clinical pharmacology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
R F Schafers H L Elliott C A Howie J L Reid 《British journal of clinical pharmacology》1992,34(6):521-526
1. The alpha 2-adrenoceptor antagonist activity of L-659,066 has been investigated in studies of healthy normotensive males to whom doses of up to 8 mg were administered by short intravenous infusion. 2. L-659,066 had no effect on basal levels of glucose or insulin and no significant effect on the plasma glucose and plasma insulin time profiles following an intravenous glucose load. 3. There was a non-significant trend for plasma noradrenaline concentrations to be higher after L-659,066. 4. L-659,066 had no significant effects on mood changes or on physical symptom scores. 5. There were no significant effects on supine blood pressure but there were consistent increases in heart rate both supine (non-significant) and erect (P < 0.01). 6. Ex vivo platelet aggregation studies confirmed alpha 2-adrenoceptor antagonist activity with L-659,066 but with an approximately 9-fold lesser potency than yohimbine. 7. While L-659,066 has alpha 2-adrenoceptor antagonist activity these results suggest that it is unlikely to present a new therapeutic approach for improving insulin release. 相似文献
63.
64.
Anti-peptide antibodies to cathepsins B, L and D and type IV collagenase. Specific recognition and inhibition of the enzymes. 总被引:1,自引:0,他引:1
T H Coetzer E Elliott P H Fortgens R N Pike C Dennison 《Journal of immunological methods》1991,136(2):199-210
Anti-peptide antibodies were raised against synthetic peptides selected from the sequences of human cathepsins B and L, porcine cathepsin D and human type IV collagenase. Sequences were selected from the active site clefts of the cathepsins in the expectation that these would elicit immunoinhibitory antibodies. In the case of type IV collagenase a sequence unique to this metalloproteinase subclass and suitable for immunoaffinity purification, was chosen. Antibodies against the chosen cathepsin B sequence were able to recognize the peptide but were apparently unable to recognise the whole enzyme. Antibodies against the chosen cathepsin L sequence were found to recognise and inhibit the native enzyme and were also able to discriminate between denatured cathepsins L and B on Western blots. Antibodies against the chosen cathepsin D sequence recognised native cathepsin D in a competition ELISA, but did not inhibit the enzyme. Native type IV collagenase was purified from human leukocytes by immuno-affinity purification with the corresponding anti-peptide antibodies. 相似文献
65.
66.
67.
Proper timing of surgery for gallstone pancreatitis 总被引:23,自引:0,他引:23
68.
Trehalose dimycolate enhances resistance to infection in neutropenic animals. 总被引:2,自引:0,他引:2
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![点击此处可从《Infection and immunity》网站下载免费的PDF全文](/ch/ext_images/free.gif)
G S Madonna G D Ledney T B Elliott I Brook J T Ulrich K R Myers M L Patchen R I Walker 《Infection and immunity》1989,57(8):2495-2501
Bacterial infections are lethal complications of neutropenia, and antibiotics alone are inadequate therapy for these infections. Irradiated mice become severely neutropenic and remain susceptible to infection for 2 to 3 weeks, depending on the dose and quality of radiation. Some bacterial cell wall derivatives stimulate nonspecific host defense mechanisms against a variety of microbes which might cause postirradiation infection. In this study we determined if the cell wall glycolipid trehalose dimycolate (TDM), derived from Mycobacterium phlei, or a synthetic preparation of TDM was able to (i) enhance survival in mice when given before or after lethal doses of 60Co radiation and (ii) increase nonspecific resistance to postirradiation infection. Treatment with TDM oil-in-water emulsions and with synthetic TDM significantly enhanced survival before and after lethal doses of 60Co irradiation. This result correlated with the ability of TDM to reduce the translocation of intestinal bacteria and to stimulate hematopoiesis. With respect to nonspecific resistance to infection, TDM injected 1 h after sublethal irradiation increased resistance to a lethal Klebsiella pneumoniae challenge (10 50% lethal doses of K. pneumoniae in 30 days [LD50/30]) 4 or 14 days later. Increasing the dose of K. pneumoniae to 5,000 LD50/30 on day 4 overwhelmed the ability of TDM-treated mice to overcome infection. However, TDM treatment 1 h postirradiation combined with ceftriaxone antibiotic therapy (days 5 through 14) enhanced survival, even when the higher dose of bacteria (5,000 LD50/30) was used. These results indicate that in irradiated mice, TDM can be used to enhance survival and, as a potent stimulant of nonspecific resistance to infection in neutropenic mice, can act synergistically with antibiotic therapy to reduce sepsis and mortality. 相似文献
69.
M D Brewer M N Burgess R J Dorgan R L Elliott P Mamalis B R Manger R A Webster 《Journal of medicinal chemistry》1989,32(9):2058-2062
A series of 1,2,3,4,6,7,8,12b-octahydropyrazino[2,1-alpha][2] benzazepine derivatives was prepared and the cestocidal activity of the compounds evaluated in an in vitro Taenia crassiceps screen. Many of these derivatives proved to be highly active, and 2-(cyclohexylcarbonyl)-4-oxo-1,2,3,4,6,7,8,12b- octahydropyrazino[2,1-alpha][2]benzazepine, epsiprantel (BAN) (22), was selected for further development. The structure-activity relationships are discussed. 相似文献
70.
Introduction : Hypertrophic scar is a devastating sequel to burns and other tangential skin injuries. It follows deep dermal injuries and does not occur after superficial injuries. Nitric oxide (NO) plays many important roles in wound healing from inflammation to scar remodeling. Studies have shown that expression of nitric oxide synthase and nitric oxide production are decreased in human hypertrophic scar. However little is known about NO involvement in the early stages of hypertrophic scarring, because of the lack of an animal model. It was recently reported that the female red Duroc pig (FRDP) makes thick scar, which is similar to human hypertrophic scar. We hypothesized that NO production in wounds on the female, red Duroc pig is similar to that of human hypertrophic scar and that NO involvement in deep wounds is different from that in superficial wounds. Methods : Superficial (0.015” to 0.030”) and deep (0.045” to 0.060”) wounds were created on the backs of four FRDPs. Biopsies were collected at weeks 1.5, 4, 8 and 21 post wounding including samples of uninjured skin. Nitric oxide levels were measured with the Griess reaction assay and normalized with tissue protein level. Results : Superficial wounds healed with an invisible scar whereas the deep wounds healed with scar resembling mild hypertrophic scar. The thickness of the scars from the deep wounds was significantly greater than uninjured skin and healed superficial wounds (p < 0.01). NO levels were increased at 1.5 weeks in deep wounds compared to superficial wounds and uninjured skin (p < 0.05). At 8 weeks, NO levels in deep wounds had returned to the level of uninjured tissue and superficial wounds. By 21 weeks, NO levels had decreased significantly when compared to superficial wounds (p < 0.01). There were no differences in NO levels between uninjured skin and superficial wounds at any time point (p > 0.05). Conclusions : NO production is similar in late, deep wounds on the female, red Duroc pig to that reported in the literature for human hypertrophic scar further validating this animal model. NO production is quite different after deep wounds as compared to superficial wounds in the FRDP. Early elevation in nitric oxide production might account for excessive inflammation in deep wounds that become thick scars in the FRDP. Nitric oxide regulators and effects at early stages of scar formation should be elucidated further and the FRDP appears to be a useful model. 相似文献