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561.
Genetic analysis is consistent with the hypothesis that NF1 limits myeloid cell growth through p21ras 总被引:6,自引:7,他引:6
Children with neurofibromatosis, type 1 (NF-1) are at increased risk of developing malignant myeloid disorders and their bone marrows frequently show loss of the normal allele of the NF1 tumor-suppressor gene. NF1 encodes a protein called neurofibromin, which accelerates guanosine triphosphate (GTP) hydrolysis on the p21ras (Ras) family of signaling proteins. We used a genetic approach to test the hypothesis that NF1 negatively regulates myeloid cell growth through its effect on Ras. This model predicts that, if RAS mutations and loss of NF1 function deregulate myeloid growth by the same biomechanical mechanism, then activating RAS mutations will be restricted to children with malignant myeloid disorders who do not have NF-1. We studied 71 children, including 28 with bone marrow monosomy 7 syndrome (Mo7), 35with juvenile chronic myelogenous leukemia (JCML), three with other forms of preleukemia, and five with acute myelogenous leukemia (AML), for activating mutations of KRAS and NRAS. The incidence of RAS mutations was 21% (12 of 55) in patients without NF-1 and 0% (zero of 16) in children with NF-1 (P = .04). Among the 55 patients who did not have NF-1, we found RAS mutations in four of 27 with Mo 7, in five of 24 with JCML, in two of 3 with AML, and in a patient with myeloproliferative syndrome (MPS). These data from primary human cancer cells provide strong genetic evidence that NF1 limits the growth of myeloid cells by regulating Ras. 相似文献
562.
563.
Background
Primary Cytomegalovirus (CMV) infection during pregnancy is a frequent and serious threat to the fetus. As there is no vaccine alternative measures are needed to prevent congenital CMV infection.Objective
This study determined CMV Immunoglobulin G (IgG) antibody among pregnant women in order to ascertain the immune status of mothers to guide policy makers.Methods
A semi-structured questionnaire was initially administered to obtain information on demographic details, stage of pregnancy and risk factors. Blood was collected by venipuncture from 180 women attending the antenatal clinic in Murtala Mohammed Specialist Hospital Kano, Kano State, Nigeria. Sera samples were screened using CMV IgG ELISA kit (Dialab, Austria).Results
Out of 180 pregnant women, 164 (91.1%) were seropositive. Based on stages of pregnancy 6/6(100%), 52/60(86.7%) and 106/114(93.0%) were seropositive among women in the first, second and third trimesters respectively.Conclusion
Seroprevalence of pregnant women to CMV Ig G is high, hence the need for CMV - IgM screening to know the extent of active infection. There is also need for public enlightenment on the methods of transmission, effective prevention and control strategies. 相似文献564.
Raman Jay RR McKay L Werner MB Atkins EM Van Allen KM Olivier J Song S Signoretti DF McDermott TK Choueiri 《Urologic oncology》2017,35(3):117-118
Background
Sarcomatoid renal cell carcinoma (RCC) is associated with an aggressive biology and a poor prognosis. Poor-risk RCC is defined by clinical prognostic factors and demonstrates similarly aggressive behavior. No standard treatment exists for patients with sarcomatoid RCC, and treatment options for patients with poor-risk disease are of limited benefit. The objective of this study was to investigate the efficacy of antiangiogenic therapy in combination with cytotoxic chemotherapy in clinically aggressive RCC.Methods
This was a phase 2, single-arm trial of sunitinib and gemcitabine in patients with sarcomatoid or poor-risk RCC. The primary end point was the objective response rate (ORR). Secondary end points included the time to progression (TTP), overall survival (OS), safety, and biomarker correlatives.Results
Overall, 39 patients had sarcomatoid RCC, and 33 had poor-risk RCC. The ORR was 26% for patients with sarcomatoid RCC and 24% for patients with poor-risk RCC. The median TTP and OS for patients with sarcomatoid RCC were 5 and 10 months, respectively. For patients with poor-risk disease, the median TTP and OS were 5.5 and 15 months, respectively. Patients whose tumors had>10% sarcomatoid histology had a higher clinical benefit rate (ORR plus stable disease) than those with≤10% sarcomatoid histology (P = 0.04). The most common grade 3 or higher treatment-related adverse events included neutropenia (n = 20), anemia (n = 10), and fatigue (n = 7).Conclusions
These results suggest that antiangiogenic therapy and cytotoxic chemotherapy are an active and well-tolerated combination for patients with aggressive RCC. The combination may be more efficacious than either therapy alone and is currently under further investigation. 相似文献565.
Michelle J Alfa Evelyn Lo Alana Wald Christine Dueck Pat DeGagne Godfrey KM Harding 《BMC infectious diseases》2010,10(1):268
Background
C. difficle spores in the environment of patients with C. difficile associated disease (CDAD) are difficult to eliminate. Bleach (5000 ppm) has been advocated as an effective disinfectant for the environmental surfaces of patients with CDAD. Few alternatives to bleach for non-outbreak conditions have been evaluated in controlled healthcare studies. 相似文献566.
Oral Diseases (2010) 16 , 769–773 Objective: The aim of this work was to determine the frequency and nature of oral manifestations secondary to use of cardiovascular drugs. Methods: Five hundred and thirty one patients attending an adult cardiology clinic in Saudi Arabia were questioned about the occurrence of oral dryness, dysgeusia, or burning sensation and were clinically evaluated for the presence of oral mucosal or gingival disease. Data were statistically analyzed with chi‐squared tests, odds ratios and Student’s t‐test. Results: Oral symptoms and/or signs were recorded in 75 (14.1%) patients with xerostomia being the most common (7.5%), followed by lichenoid (lichen planus‐like) lesions (3.6%) and dysgeusia (1.9%). Xerostomia was significantly more frequent in patients with a history of diabetes mellitus and in female patients (P < 0.05). There were no statistically significant differences (P > 0.05) between patients with or without oral manifestations when age, gender, cardiovascular risk factor, cardiac disease, type of cardiac drug used or the number of medications were assessed. There was a trend for xerostomia to be less frequent in patients receiving therapy with angiotensin converting enzyme inhibitors and a slight trend of xerostomia to be more likely with increased number of non‐cardiac and total number of agents per subject. The number of non‐cardiac and total medications taken by patients with potential oral manifestations tended to be greater than that of patients without oral manifestations. Conclusions: The frequency of potential oral manifestations in patients receiving cardiovascular agents was 14.1%. The occurrence and character of the oral manifestations had no significant relation with individual cardiac drugs, although there was a trend for oral manifestations to be likely with increasing number of drugs. 相似文献
567.
X Zhang T YY Lai S WY Chiang P OS Tam D TL Liu C KM Chan C P Pang C Zhao L J Chen 《Eye (London, England)》2013,27(10):1204-1213
Purpose
Mutations in the SNRNP200 gene have been reported to cause autosomal dominant retinitis pigmentosa (adRP). In this study, we evaluate the mutation profile of SNRNP200 in a cohort of southern Chinese RP patients.Methods
Twenty adRP patients from 11 families and 165 index patients with non-syndromic RP with mixed inheritance patterns were screened for mutations in the mutation hotspots of SNRNP200. These included exons 12–16, 22–32, and 38–45, which covered the two helicase ATP-binding domains in DEAD-box and two sec-63 domains. The targeted regions were amplified by polymerase chain reaction and analyzed by direct DNA sequencing, followed by in silico analyses.Results
Totally 26 variants were identified, 18 of which were novel. Three non-synonymous variants (p.C502R, p.R1779H and p.I698V) were found exclusively in patients. Two of them, p.C502R and p.R1779H, were each identified in one simplex RP patient, whereas p.I698V occurred in one patient with unknown inheritance pattern. All three residues are highly conserved in SNRNP200 orthologs. Nevertheless, only p.C502R and p.R1779H were predicted to affect protein function by in silico analyses, suggesting these two variants are likely to be disease-causing mutations. Notably, all mutations previously identified in other study populations were not detected in this study.Conclusions
Our results reveal a distinct mutation profile of the SNRNP200 gene in a southern Chinese cohort of RP patients. The identification of two novel candidate mutations in two respective patients affirmed that SNRNP200 contributes to a proportion of overall RP. 相似文献568.
569.
Krpan KM Levine B Stuss DT Dawson DR 《Journal of clinical and experimental neuropsychology》2007,29(1):36-46
The purpose of this study was to examine the relationship between executive function and coping at one-year-post traumatic brain injury (TBI). TBI and matched control groups completed a coping questionnaire and a neuropsychological test series. In the TBI group, better executive performance was related to the use of problem focused coping (considered more adaptive). Conversely, lower executive performance was related to the use of emotion focused coping (considered more maladaptive). Planned hierarchical regression showed that executive function contributed significantly to the use of problem focused coping above and beyond pre-morbid intelligence and injury severity. Implications for cognitive rehabilitation are discussed. 相似文献
570.
CE Beyer Q Lin B Platt J Malberg G Hornby KM Sullivan DL Smith T Lock PJ Mitchell NT Hatzenbuhler DA Evrard BL Harrison R Magolda MN Pangalos LE Schechter S Rosenzweig-Lipson TH Andree 《British journal of pharmacology》2009,157(2):307-319