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941.
Ethnopharmacological relevance
Amazonian peoples utilize a variety of psychoactive plants that may contain novel biologically active compounds. Efforts to investigate such remedies in terms of neuropharmacology have been limited.Aim of this study
This study identified Amazonian ethnomedicines with potential for the treatment of cognitive deficits in schizophrenia and dementias, and characterized their interactions with CNS neurotransmitter receptors in vitro.Materials and methods
Approximately 300 Amazonian species with folk uses or constituents indicative of central nervous system activity were incorporated into a database constructed from literature searches, herbarium surveys, and interviews with traditional practitioners. Approximately 130 of these targeted species were collected in Loreto province, Peru, and 228 fractions derived from them were screened in 31 radioreceptor assays via the resources of the NIMH Psychoactive Drug Screening Program. A subset was also screened in functional assays at selected serotonin, muscarinic, and adrenergic receptors.Results
Ninety-one samples displayed ≥60% inhibition of radioligand binding activity in receptor assays; 135 samples displayed agonist or antagonist activity (or both) in functional assays.Conclusions
Potential CNS activity was detected in about 40% of the samples screened, with some correlations to both folk uses and phytochemical constituents. These results may point to novel and potentially therapeutic CNS active compounds. 相似文献942.
Carina Roth Klaus Pantel Volkmar Müller Brigitte Rack Sabine Kasimir-Bauer Wolfgang Janni Heidi Schwarzenbach 《BMC cancer》2011,11(1):4
Background
As cell-free circulating DNA exists predominantly as mono- and oligonucleosomes, the focus of the current study was to examine the interplay of circulating nucleosomes, DNA, proteases and caspases in blood of patients with benign and malignant breast diseases. 相似文献943.
944.
Ali Al-Ahmad Dominik Roth Martin Wolkewitz Margit Wiedmann-Al-Ahmad Marie Follo Petra Ratka-Krüger Daniela Deimling Elmar Hellwig Christian Hannig 《Clinical oral investigations》2010,14(4):391-396
The aim of the study was to monitor changes in oral health and oral biofilm composition in vivo during an experiment simulating prehistoric lifestyle and diet and poor oral hygiene. Thirteen subjects lived for a period of 8 weeks under Neolithic conditions. The following clinical parameters were recorded before and after the project: gingival and plaque index (Löe and Silness, Acta Odontol Scand 21:533, 1963; Silness and Löe, Acta Odontol Scand 22:121–135, 1964), probing pocket depth, and bleeding upon probing. In addition, supragingival plaque samples were collected both before and after the project and were analysed quantitatively using multiplex fluorescence in situ hybridization and confocal laser scanning microscopy. The following plaque bacteria were evaluated: Streptococcus spp., Veillonella spp., Fusobacterium nucleatum, and Actinomyces naeslundii. The plaque index increased significantly from 1.12 up to 1.55 over the 8-week period (gingival index before, 0.46; after, 0.93; p < 0.05). A strong correlation of both indices was recorded before (r = 0.77) and after (r = 0.83) participation in the study. Each of the children in the study showed a progression of carious lesions and/or new areas of demineralisation. The probing pocket depth and bleeding upon probing were not affected. All subjects yielded an intra-individual shift in biofilm composition. The proportion of F. nucleatum decreased across all subjects. The proportion of Veillonella spp. increased among the children. Poor oral hygiene and change of diet lead to an increase in oral plaque and gingival inflammation. The inter-individual comparison indicated a shift in bacterial composition. 相似文献
945.
946.
947.
Enhanced amylin-mediated body weight loss in estradiol-deficient diet-induced obese rats 总被引:1,自引:0,他引:1
Trevaskis JL Turek VF Wittmer C Griffin PS Wilson JK Reynolds JM Zhao Y Mack CM Parkes DG Roth JD 《Endocrinology》2010,151(12):5657-5668
In rodents, ovariectomy (OVX) elicits weight gain and diminished responsiveness to homeostatic signals. Here we characterized the response of obese OVX rats to peripheral amylin. Rats received sham surgery (SHAM), OVX, or OVX with hormonal replacement (17β-estradiol, 2 μg per 4 d; OVX+E) and were infused with vehicle or amylin (50 μg/kg · d) for 28 d. Amylin reduced body weight (5.1 ± 1.1%) and food intake (10.9 ± 3.4%) in SHAM rats but was twice as efficacious in OVX rats in reducing weight (11.2 ± 1.9%) and food intake (23.0 ± 2.0%). There were no differences between amylin-treated SHAM and OVX+E rats. OVX decreased metabolic rate (~24%) and increased respiratory exchange ratio relative to SHAM. Amylin partially normalized metabolic rate (13% increase) in OVX rats and decreased respiratory exchange ratio in OVX and SHAM rats. Regarding central mechanisms, amylin infusion corrected the OVX-induced decrease in hippocampal neurogenesis and increased immobility in the forced swim test. Additionally, amylin increased neurogenesis (~2-fold) within the area postrema of OVX rats. To assess the contribution of endogenous leptin to amylin-mediated weight loss in OVX rats, amylin was administered to SHAM or OVX Zucker diabetic fatty rats. In SHAM rats, amylin infusion reduced food intake but not body weight, whereas in OVX Zucker diabetic fatty rats, food intake, body weight, and insulin were reduced. Overall, amylin induced greater body weight loss in the absence of estradiol via central and peripheral actions that did not require leptin. These findings support the clinical investigation of amylin in low estradiol (e.g. postmenopausal) states. 相似文献
948.
Christian L. Roth Pablo J. Enriori Ursel Gebhardt Hermann L. Müller Thomas Reinehr 《Metabolism: clinical and experimental》2010,59(2):186-1991
Relationships of blood circulating melanocortins to childhood obesity are not well established. We evaluated serum α-melanocyte-stimulating hormone (α-MSH) in lean children and different study groups of childhood obesity. We examined serum α-MSH in 52 otherwise healthy children with childhood obesity (Ob; mean age, 11 years; 32 girls/20 boys), 27 normal-weight children of same age, 7 additional obese patients with reduced melanocortin-4 receptor function (MC4Rmut), and 22 patients with craniopharyngioma (CP). Fasting serum α-MSH and leptin were measured by radioimmunoassay. Serum α-MSH was also evaluated 1 hour after 500-kcal liquid meal (CP and Ob) and at the end of 1-year lifestyle intervention in 24 Ob patients. The α-MSH levels were similar in obese vs lean children but significantly lower in CP (P< .001) and significantly higher (P < .05) in MC4Rmut patients compared with Ob. One hour after liquid meal, α-MSH increased in patients with Ob but not with CP. After 1 year, α-MSH levels increased significantly in the successful weight reduction Ob subgroup despite unchanged cortisol levels. The α-MSH changes correlated to weight status changes (r = 0.67, P = .0003) but not to changes of cortisol, insulin, or homeostasis model assessment of insulin resistance index. Persistently low α-MSH levels in CP patients are suspected to be due to pituitary or hypothalamic damage. High peripheral levels in MC4Rmut carriers indicate up-regulation of α-MSH. Changes of weight status are associated with changes of peripheral α-MSH. 相似文献
949.
Sharad S. Singhal Cherice Roth Kathryn Leake Jyotsana Singhal Sushma Yadav Sanjay Awasthi 《Biochemical pharmacology》2009,77(6):1074-1083
RLIP76 plays a central role in radiation and chemotherapy resistance through its activity as a multi-specific ATP-dependent transporter which is over-expressed in a number of types of cancers. RLIP76 appears to be necessary for cancer cell survival because both in vitro cell culture and in vivo animal tumor studies show that depletion or inhibition of RLIP76 causes selective toxicity in malignant cells. RLIP76 induces apoptosis in cancer cells through the accumulation of endogenously formed GS-E. The results of our in vivo studies demonstrate that administration of RLIP76 antibodies, siRNA or anti-sense to mice bearing xenografts of PC-3 prostate cancer cells leads to near complete regression of established subcutaneous xenografts with no apparent toxic effects. Since anti-RLIP76 IgG (which inhibit RLIP76-mediated transport), siRNA and antisense (which deplete RLIP76) showed similar tumor regressing activities, our results indicate that the inhibition of RLIP76 transport activity at the cell surface is sufficient for observed anti-tumor activity. These studies indicate that RLIP76 serves a key effector function for the survival of prostate cancer cells and that it is a valid target for cancer therapy. 相似文献
950.
This study aimed to investigate if the absorption of the human African trypanosomiasis agent eflornithine was stereospecific and dose dependent after oral administration. Male Sprague-Dawley rats were administered single doses of racemic eflornithine hydrochloride as an oral solution (750, 1,500, 2,000, or 3,000 mg/kg of body weight) or intravenously (375 or 1,000 mg/kg of body weight). Sparse blood samples were obtained for determination of eflornithine enantiomers by liquid chromatography with evaporative light-scattering detection (lower limit of quantification [LLOQ], 83 microM for 300 microl plasma). The full plasma concentration-time profile of racemic eflornithine following frequent sampling was determined for another group of rats, using a high-performance liquid chromatography-UV method (LLOQ, 5 microM for 50 microl plasma). Pharmacokinetic data were analyzed in NONMEM for the combined racemic and enantiomeric concentrations. Upon intravenous administration, the plasma concentration-time profile of eflornithine was biphasic, with marginal differences in enantiomer kinetics (mean clearances of 14.5 and 12.6 ml/min/kg for L- and D-eflornithine, respectively). The complex absorption kinetics were modeled with a number of transit compartments to account for delayed absorption, transferring the drug into an absorption compartment from which the rate of influx was saturable. The mean bioavailabilities for L- and D-eflornithine were 41% and 62%, respectively, in the dose range of 750 to 2,000 mg/kg of body weight, with suggested increases to 47% and 83%, respectively, after a dose of 3,000 mg/kg of body weight. Eflornithine exhibited enantioselective absorption, with the more potent L-isomer being less favored, a finding which may help to explain why clinical attempts to develop an oral treatment have hitherto failed. The mechanistic explanation for the stereoselective absorption remains unclear. 相似文献