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71.
DNA polymerase beta mutations in human colorectal cancer. 总被引:15,自引:0,他引:15
Increasing numbers of alterations have been found in protooncogenes (e.g., ras, myc), as well as tumor suppressor genes (e.g., p53, Rb) in various types of tumors. The multiple mutations cannot be explained by the spontaneous mutation rate. It has been suggested that mutator phenotypes leading to the accumulation of these mutations may be required in the early stages of tumorigenesis. To test this hypothesis, the entire coding region of DNA polymerase beta, a repair enzyme, mRNA from colorectal tumors, and corresponding normal mucosa were amplified by polymerase chain reaction, cloned, and sequenced. Mutations in the catalytic domain of DNA polymerase beta were detected in colorectal tumor specimens compared to the normal colorectal mucosa, placenta, and blood samples. Since these mutations changed the structure of polymerase beta, it is expected that the efficiency of the DNA repair system would be impaired and thus may account for the high mutation rate observed in colorectal carcinomas. 相似文献
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Early mobilisation after percutaneous cardiac catheterisation using collagen plug (VasoSeal) haemostasis. 下载免费PDF全文
OBJECTIVE--To assess the efficacy and safety of a haemostatic bovine collagen plug (VasoSeal) in reducing patient immobilisation after cardiac catheterisation from a percutaneous femoral arterial approach. DESIGN--A non-randomised, prospective analysis of a new biodegradable haemostatic agent on an intention to treat basis. SETTING--The catheterisation suite of a regional cardiothoracic unit. PATIENTS--A series of 63 patients having various diagnostic investigations and therapeutic interventions agreed to participate in this study. INTERVENTIONS--Cardiac catheterisation was performed from a percutaneous femoral artery approach. Patients taking aspirin and those who required formal anticoagulation were not excluded. Patients were measured for the appropriate sized collagen delivery system at the beginning of the procedure. At the end of the procedure two bovine collagen plugs were applied to the surface of the femoral artery through the channel created by the application device. MAIN OUTCOME MEASURES--Incidence of successful delivery, insertion time, immediate outcome, inpatient complications, success of mobilisation of the patient at one and two hours after the procedure, and whether these variables relate to individual patient characteristics. RESULTS--Successful placement of the device was achieved in 57 of 63 consecutive patients (90.5%). The mean (SD) insertion time was 86 (24) seconds. Six (9.5%) patients did not receive the haemostat because of femoral artery perforation by the tissue dilator (n = 3), inability to compress the femoral artery proximal to the site of delivery (n = 1), pre-existing haematoma (n = 1), or patient withdrawal from the study (n = 1). Uncomplicated mobilisation within two hours of investigation was possible in 54 of 57 (94.7%) patients receiving this device. A sizeable haematoma (> 5 x 5 cm) prevented early mobilisation in the remaining three patients. Mobilisation was uncomplicated in 32 of 34 (94.1%) patients mobilised at two hours and 22 of 23 (95.6%) at one hour (NS). One patient who was mobilised early without complication later developed evidence of claudication in the treated leg. Femoral arteriography showed a smooth intraluminal filling defect attached to the wall of the femoral artery at the puncture site. This obstruction, presumed to be a collagen plug, was treated successfully with angioplasty. Sheath size, arterial pressure, the use of aspirin, heparin or warfarin, and body mass index did not influence patient outcome. The pattern of complications did not relate to a learning curve experience. CONCLUSIONS--The bovine collagen haemostat is a relatively safe and effective device that allows far earlier patient mobilisation than conventional haemostasis after diagnostic and therapeutic interventions from a percutaneous femoral artery approach. These results have important implications for patients undergoing investigation in mobile x ray units or in hospital based day case units. 相似文献
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T lymphocyte subsets were determined in 12 patients with untreated systemic lupus erythematosus (SLE) and in 14 healthy controls. Six out of 8 (75%) patients with lupus nephritis had reduction in the percentage of T helper cells and low helper: suppressor cell ratios compared with controls. None of the 4 patients without nephritis had low ratios. Cold-reactive anti-lymphocyte antibodies cytotoxic to both the helper and the suppressor cells were detected in 7 of the 8 patients who had nephritis. Low T helper: suppressor cell ratio in SLE seems to correlate with the presence of active nephritis. 相似文献
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Despite the wide clinical use of lithium in the treatment of manic depressive illness there is no adequate explanation for its mechanism of action. In the light of lithium's suggestive effects on the second messenger system in the brain, we studied the effects of chronic dietary lithium treatment (achieving blood levels in the therapeutic range) on protein phosphorylation in different areas of rat brain. An increase in the phosphorylation of a 64-kDa membrane-associated protein was evident in the lithium-treated rats compared to controls. This increase was observed only under basal phosphorylating conditions and was abolished when the phosphorylation was performed in the presence of Ca2+ or Ca2+ and calmodulin. The possibility that this 64-kDa protein affected by lithium is the beta-subunit of the calmodulin-dependent protein kinase or a different protein which co-migrates with it is discussed. 相似文献
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S Shaunak L Ang K Colston S Patel M Bland J D Maxwell 《Clinical science (London, England : 1979)》1987,73(5):541-546
1. The maximum voluntary isometric contraction (MVC) of the dominant quadriceps muscle was measured in 136 healthy White and 172 healthy Hindu Asian subjects resident in London, using a specially designed chair equipped with a force measuring load cell. 2. Males were stronger than females, and for both sexes MVC declined with age. From age 20 to 60 the annual decline in MVC ranged from 0.56% in White males to 1.5% in female Asians. 3. White subjects were stronger than Asian subjects even after correcting for the effect of age, height, weight and sex in a multi-factorial analysis. 4. Only in males did MVC correlate with height and weight. Asian women were more obese than any other group, and showed an increase in body mass index with age. 5. Twenty-two per cent of Asian subjects had marked vitamin D deficiency (plasma 25-hydroxycholecalciferol less than 10 nmol/1). There was no correlation between MVC, and plasma 25-hydroxycholecalciferol. 相似文献