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991.
Werner F. Helsen Florian Van Halewyck Oron Levin Matthieu P. Boisgontier Ann Lavrysen Digby Elliott 《Age (Dordrecht, Netherlands)》2016,38(2):45
The present study examines whether non-active older adults are more dependent on visual information when executing aiming movements and whether age-related declines in proprioception play a mediating role herein. Young (N = 40) and older adults (N = 38) were divided into physically active and non-active subgroups based on self-reported sports participation levels. In experiment 1, participants executed wrist-aiming movements with and without visual feedback. In experiment 2, passive proprioceptive acuity was assessed using wrist motion detection and position matching tests. Results showed similar aiming accuracy across age groups both with and without visual feedback, but older adults exhibited longer movement times, prolonged homing-in phase, and made more corrective submovements. Passive proprioceptive acuity was significantly affected by physical activity level and age, with participants in the active group scoring better than their non-active peers. However, these declines did not predict performance changes on the aiming task. Taken together, our observations suggest that decline in proprioceptive acuity did not predict performance changes on the aiming task and older adults were able to compensate for their decreased motion and position sense when allowed sufficient time. In line with these observations, we proposed that older adults are able to compensate for their decline in proprioception by increasing their reliance on predictive models. 相似文献
992.
993.
Milton Packer William T Abraham Mandeep R Mehra Clyde W Yancy Christine E Lawless Judith E Mitchell Frank W Smart Rachel Bijou Christopher M O'Connor Barry M Massie Ileana L Pina Barry H Greenberg James B Young Daniel P Fishbein Paul J Hauptman Robert C Bourge John E Strobeck Srinvivas Murali Douglas Schocken John R Teerlink Wayne C Levy Robin J Trupp Marc A Silver 《Journal of the American College of Cardiology》2006,47(11):2245-2252
OBJECTIVES: This study sought to assess the potential utility of impedance cardiography (ICG) in predicting clinical deterioration in ambulatory patients with heart failure (HF). BACKGROUND: Impedance cardiography uses changes in thoracic electrical impedance to estimate hemodynamic variables, but its ability to predict clinical events has not been evaluated. METHODS: We prospectively evaluated 212 stable patients with HF and a recent episode of clinical decompensation who underwent serial clinical evaluation and blinded ICG testing every 2 weeks for 26 weeks and were followed up for the occurrence of death or worsening HF requiring hospitalization or emergent care. RESULTS: During the study, 59 patients experienced 104 episodes of decompensated HF (16 deaths, 78 hospitalizations, and 10 emergency visits). Multivariate analysis identified 6 clinical and ICG variables that independently predicted an event within 14 days of assessment. These included three clinical variables (visual analog score, New York Heart Association functional class, and systolic blood pressure) and three ICG parameters (velocity index, thoracic fluid content index, and left ventricular ejection time). The three ICG parameters combined into a composite score was a powerful predictor of an event during the next 14 days (p = 0.0002). Visits with a high-risk composite score had 2.5 times greater likelihood and those with a low-risk score had a 70% lower likelihood of a near-term event compared with visits at intermediate risk. CONCLUSIONS: These results suggest that when performed at regular intervals in stable patients with HF with a recent episode of clinical decompensation, ICG can identify patients at increased near-term risk of recurrent decompensation. 相似文献
994.
Acromegaly is a debilitating disease usually caused by a growth-hormone secreting pituitary adenoma. Therapeutic goals include
improvement of symptoms, reduction in tumor mass, biochemical normalization, and preservation of pituitary function. Treatment
options include transsphenoidal surgery, radiation, and pharmacotherapy. In view of the good cure rate, surgery remains the
therapeutic modality of choice for most patients with microadenomas or well-circumscribed macroadenomas. In contrast, >40%
of patients with invasive macroadenomas (who make up the majority of patients with acromegaly) will have residual disease
following surgery, and require additional therapeutic intervention. Somatostatin analogs result in biochemical normalization
in >60% of non-operated patients, and are well tolerated. Therefore, somatostatin analogs have emerged as a rational first-line
treatment for the appropriately selected patient with acromegaly. 相似文献
995.
A Sertoli cell-selective knockout of the androgen receptor causes spermatogenic arrest in meiosis 总被引:15,自引:0,他引:15 下载免费PDF全文
De Gendt K Swinnen JV Saunders PT Schoonjans L Dewerchin M Devos A Tan K Atanassova N Claessens F Lécureuil C Heyns W Carmeliet P Guillou F Sharpe RM Verhoeven G 《Proceedings of the National Academy of Sciences of the United States of America》2004,101(5):1327-1332
Androgens control spermatogenesis, but germ cells themselves do not express a functional androgen receptor (AR). Androgen regulation is thought to be mediated by Sertoli and peritubular myoid cells, but their relative roles and the mechanisms involved remain largely unknown. Using Cre/loxP technology, we have generated mice with a ubiquitous knockout of the AR as well as mice with a selective AR knockout in Sertoli cells (SC) only. Mice with a floxed exon 2 of the AR gene were crossed with mice expressing Cre recombinase ubiquitously or selectively in SC (under control of the anti-Müllerian hormone gene promoter). AR knockout males displayed a complete androgen insensitivity phenotype. Testes were located abdominally, and germ cell development was severely disrupted. In contrast, SC AR knockout males showed normal testis descent and development of the male urogenital tract. Expression of the homeobox gene Pem, which is androgen-regulated in SC, was severely decreased. Testis weight was reduced to 28% of that in WT littermates. Stereological analysis indicated that the number of SC was unchanged, whereas numbers of spermatocytes, round spermatids, and elongated spermatids were reduced to 64%, 3%, and 0% respectively of WT. These changes were associated with increased germ cell apoptosis and grossly reduced expression of genes specific for late spermatocyte or spermatid development. It is concluded that cell-autonomous action of the AR in SC is an absolute requirement for androgen maintenance of complete spermatogenesis, and that spermatocyte/spermatid development/survival critically depends on androgens. 相似文献
996.
MELD score as a predictor of pretransplant and posttransplant survival in OPTN/UNOS status 1 patients 总被引:12,自引:0,他引:12
Kremers WK van IJperen M Kim WR Freeman RB Harper AM Kamath PS Wiesner RH 《Hepatology (Baltimore, Md.)》2004,39(3):764-769
The Model for End-Stage Liver Disease (MELD) score is predictive of survival and is used to prioritize patients with chronic liver disease patients for orthotopic liver transplantation (OLT). The aims of this study are (1) to assess the ability of MELD score at listing to predict pretransplant and posttransplant survival for nonchronic liver disease patients listed with the Organ Procurement and Transplantation Network/ United Network for Organ Sharing (OPTN/UNOS) as Status 1; and (2) to compare survival associated with 4 diagnostic groups within the Status 1 designation. The study population consisted of adult patients listed for OLT at Status 1 in the UNOS national database between November 1, 1999 and March 14, 2002 (N = 720). Events within 30 days of listing were analyzed using Kaplan-Meier and Cox regression methodology. Patients meeting criteria for fulminant hepatic failure without acetaminophen toxicity (FHF-NA, n = 312) had the poorest survival probability while awaiting OLT; this was negatively correlated with MELD score (P =.0001). These patients experienced the greatest survival benefit associated with OLT, with an estimated improvement of survival from about 58% to 91% (P <.0001). Patients listed for primary nonfunction within 7 days of OLT (n = 268) did not show mortality to be related to MELD score (P =.41) and did not show a significant association between survival and OLT (P =.68). In conclusion, liver allocation within the Status 1 designation may need to be further stratified by diagnosis, and MELD score may be useful for prioritizing FHF-NA candidates. 相似文献
997.
Harrison J; Kappas A; Levere RD; Lutton JD; Chertkov JL; Jiang S; Abraham NG 《Blood》1993,82(12):3574-3579
The ability of combination treatment with erythropoietin (Epo) and heme to rescue hematopoietic activity in mice from the suppressive effect of azidothymidine (AZT) was determined. Exposure of mice to AZT for 5 weeks produced marked anemia, thrombocytopenia, neutropenia, and weight loss, whereas mice that received Epo and heme for 3 subsequent weeks showed significant alleviation of AZT cytotoxicity. Treatment with Epo (10 U for 5 times/week) stimulated hematopoietic recovery in the AZT- treated animals and reduced the severe anemia and thrombocytopenia by 3 weeks. Administration of a lower Epo dose (1 U Epo) resulted in only a modest retardation of AZT-induced anemia, although, when combined with heme, there was a great improvement in recovery of erythropoiesis. The combination of heme with Epo (10 U) produced the optimum response, resulting in almost normal recovery of bone marrow cellularity as well as recovery of burst-forming units-erythroid (BFU-E) and splenic hematopoietic progenitor content (colony-forming unit-spleen [CFU-S]) by the end of 3 weeks of post-AZT treatment. Treatment with heme alone markedly enhanced the recovery of BFU-E and CFU-S, as well as body weight post-AZT; however, this recovery was not to the extent seen in combination with Epo (10 U). Long-term bone marrow cultures (LTBMCs) established from mice exposed to AZT for 8 weeks showed a marked reduction in cellularity and this was completely alleviated when mice received heme and Epo (10 U) for 3 weeks after 5 weeks of AZT administration. The additive effect of heme and Epo was seen in BFU-E production, as well as in CFU-S production, in LTBMCs. Thus, heme exerts a significant protective effect on hematopoietic progenitors in vivo and may be of potential clinical use in combination with Epo to promote effective erythropoiesis in the setting of AZT therapy. 相似文献
998.
Abraham NG Kushida T McClung J Weiss M Quan S Lafaro R Darzynkiewicz Z Wolin M 《Circulation research》2003,93(6):507-514
Heme oxygenase-1 (HO-1) is a stress protein that has been suggested to participate in defense mechanisms against agents that may induce oxidative injury, such as heme and inflammatory molecules. Incubation of endothelial cells in a high-glucose (33 mmol/L) medium for 7 days resulted in a decrease of HO activity by 34% and a decrease in HO-1 and HO-2 proteins compared with cells exposed to low glucose (5 mmol/L) (P<0.05) or cells exposed to mannitol (33 mmol/L). Overexpression of HO-1 was coupled with an increase in HO activity and carbon monoxide synthesis, decreased cellular heme, and acceleration in all phases of the cell cycle (P<0.001). The rate of cell cycle or cell birth rate was increased by 29% (P<0.05) in cells overexpressing HO-1 but decreased by 23% (P<0.05) in cells underexpressing HO-1 compared with control cells. Exposure to high glucose significantly decreased cell-cycle progression in control cells and in cells underexpressing HO-1 but did not decrease cell-cycle progression in cells overexpressing HO-1. High glucose induced p21 and p27 in control cells but not in cells overexpressing HO-1. The addition of tin-mesoporphyrin (SnMP), an inhibitor of HO activity, reversed the HO-1-mediated decrease of p21 and p27 in cells overexpressing HO-1. These findings identify a novel effect of HO-1 on endothelial cell growth and indicate that heme metabolism and HO-1 expression regulate signaling systems in cells exposed to high glucose, which controls cell-cycle progression. 相似文献
999.
1000.
Although iron chelation therapy with deferoxamine (DFO) results in improved life expectancy of patients with thalassemia, compliance with parenteral DFO treatment is unsatisfactory, underlining the need for alternative drugs and innovative ways of drug administration. We examined the chelating potential of pyridoxal isonicotinoyl hydrazone (PIH) analogs, alone or in combination with DFO, using hypertransfused rats with labeled hepatocellular iron stores and cultured iron-loaded rat heart cells. Our in vivo studies using 2 representative PIH analogs, 108-o and 109-o, have shown that PIH analogs given orally are 2.6 to 2.8 times more effective in mobilizing hepatocellular iron in rats, on a weight-per-weight basis, than parenteral DFO administered intraperitoneally. The combined effect of DFO and 108-o on hepatocellular iron excretion was additive, and response at a dose range of 25 to 200 mg/kg was linear. In vitro studies in heart cells showed that DFO was more effective in heart cell iron mobilization than all PIH analogs studied. Response to joint chelation with DFO and PIH analogs was similar to an increase in the equivalent molar dose of DFO alone, rather than the sum of the separate effects of the PIH analog and DFO. This finding was most likely the result of iron transfer from PIH analogs to DFO, a conclusion supported directly by iron-shuttle experiments using fluorescent DFO. These findings provide a rationale for the combined, simultaneous use of iron-chelating drugs and may have useful, practical implications for designing novel strategies of iron chelation therapy. 相似文献