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51.
52.
Overcoming the innate immune response to small interfering RNA 总被引:3,自引:0,他引:3
Many types of nucleic acid, including canonical small interfering RNA (siRNA) duplexes, are potent activators of the mammalian innate immune system. Synthetic siRNA duplexes can induce high levels of inflammatory cytokines and type I interferons, in particular interferon-alpha, after systemic administration in mammals and in primary human blood cell cultures. These responses are greatly potentiated by the use of delivery vehicles that facilitate cellular uptake of the siRNA. Although the immunomodulatory effects of nucleic acids may be harnessed therapeutically, for example, in oncology and allergy applications, in many cases immune activation represents a significant undesirable side effect due to the toxicities associated with excessive cytokine release and associated inflammatory syndromes. The potential for siRNA-based drugs to be rendered immunogenic is also a cause for concern because the establishment of an antibody response may severely compromise both safety and efficacy. Clearly, there are significant implications both for the development of siRNA-based drugs and in the interpretation of gene-silencing effects elicited by siRNA. This review provides the background information required to anticipate, manage, and abrogate the immunological effects of siRNA and will assist the reader in the successful in vivo application of siRNA-based drugs. 相似文献
53.
Rokey R; Verani MS; Bolli R; Kuo LC; Ford JJ; Wendt RE; Schneiders NJ; Bryan RN; Roberts R 《Radiology》1986,158(3):771-774
The feasibility of using magnetic resonance (MR) imaging to estimate myocardial infarct size was explored in an in vitro model using only the inherent differences in contrast between infarcted and noninfarcted myocardium. Eight dogs underwent coronary occlusion; their hearts were removed 6 hours later. Estimates of T2 for normal and infarcted myocardium were derived from MR images. Infarct size was quantified anatomically using triphenyltetrazolium-chloride (TTC) staining and compared with MR estimates. The T2 values derived from the images clearly discriminated between infarcted (126 +/- 22 msec) and normal myocardium (88 +/- 10 msec, P less than .05), providing images with good contrast between normal and infarcted myocardium. Comparable differences in T2 values were also noted from spectrometric determinations. Estimates of infarct size by MR imaging compared well with TTC estimates (r = 0.98) over a wide range of infarct sizes from 3% to 29% of the left ventricular mass. These results suggest the potential for in vivo quantification of infarct size based on the inherent contrast difference between infarcted and normal myocardium. 相似文献
54.
Hall RM; Unsworth A; Wroblewski BM; Siney P; Powell NJ 《Rheumatology (Oxford, England)》1997,36(1):20-26
Charnley prostheses, retrieved at revision surgery, were studied to assess
the effects of friction on the total hip replacement procedure. Frictional
resistance was measured using the Durham hip function simulator under both
dry and lubricated conditions. The friction factor values (f) for the
explanted prostheses were found to have a non- Gaussian distribution with
medians of 0.13 [inter-quartile range (IQR) 0.10-0.16] and 0.06 (IQR
0.005-0.08) for dry and lubricated (n = 0.01 Pa s) regimes, respectively.
New Charnley prostheses had values of f equal to 0.11 +/- 0.025 and 0.04
+/- 0.01 under the same conditions, and showed no large deviation from a
Gaussian distribution. There was found to be a statistically significant
difference in the medians of the friction factors for new and retrieved
prostheses in the lubricated regime. Ingression of cement into the worn
region of the cup was found to increase the friction factor significantly
under dry conditions. There was no evidence of an increase in the friction
factor or torque for those joints that had a loose socket with respect to
those that were fixed at revision. A decrease in the frictional torque
against number of cycles undergone by the joint in vivo may indicate that a
fatigue-type process may have a role in the loosening of the socket.
However, this relationship was found not to be significant for friction
measured under lubricated conditions and it seems unlikely that the
frictional torque generated in this type of prosthesis will contribute
significantly to the long-term loosening of the socket.
相似文献
55.
56.
Colin NJ Campbell Juan Ambrosioni Jose M. Miro Anna Esteve Jordi Casabona Gemma Navarro 《AIDS care》2015,27(12):1449-1454
The objective was to produce a cascade of care for Catalonia to gain a public health perspective on the overall quality of HIV services and allow comparison with other countries. It was constructed using the Integrated Epidemiological Surveillance System of HIV in Catalonia and data from the PISCIS Cohort. Estimates of the number of people living with HIV in Catalonia are modelled using Spectrum Projection Package 2011 (UNAIDS/WHO). Totals for each stage in the cascade are obtained by applying to the preceding stage a proportion estimated from available surveillance and cohort data. Undiagnosed HIV was estimated from the European literature. The proportions retained in care, on ART and virally suppressed were derived from the PISCIS cohort. Programmatic data on ART consumption was used to validate estimates. By the end of 2011 there were about 33,000 people living with HIV in Catalonia, 71% of which had been both diagnosed and linked to care. We estimate that 61% of all HIV infected persons were retained in care, 56% were on ART and 48% were virally suppressed. These figures data are comparable, although slightly lower, than that of France or the UK. The Cascade of HIV Care in Catalonia is similar to other western European countries such as France and the UK. Direct estimates of the undiagnosed HIV population and linkage to care are desirable but the contribution of cohort data to the cascade highlights their continued importance in HIV surveillance and design of evidence-based health strategies. 相似文献
57.
Background and Rationale:
Ensuring research participants’ autonomy is one of the core ethical obligations of researchers. This fundamental principle confers on every participant the right to refuse to take part in clinical research, and the measure of the number of consent refusals could be an important metric to evaluate the quality of the informed consent process. This audit examined consent refusals among Indian participants in clinical studies done at our center.Materials and Methods:
The number of consent refusals and their reasons in 10 studies done at our center over a 5-year period were assessed. The studies were classified by the authors according to the type of participant (healthy vs patients), type of sponsor (investigator-initiated vs pharmaceutical industry), type of study (observational vs interventional), level of risk [based on the Indian Council of Medical Research (ICMR) “Ethical Guidelines for Biomedical Research on Human Participants”], available knowledge of the intervention being studied, and each patient''s disease condition.Results:
The overall consent refusal rate was 21%. This rate was higher among patient participants [23.8% vs. healthy people (14.9%); P = 0.002], in interventional studies [33.6% vs observational studies (7.5%); P < 0.0001], in pharmaceutical industry-sponsored studies [34.7% vs investigator-initiated studies (7.2%); P < 0.0001], and in studies with greater risk (P < 0.0001). The most common reasons for consent refusals were multiple blood collections (28%), inability to comply with the study protocol (20%), and the risks involved (20%).Conclusion:
Our audit suggests the adequacy and reasonable quality of the informed consent process using consent refusals as a metric.KEY WORDS: Autonomy, consent, India, reason, refusal, risk 相似文献58.
59.
International maritime health has largely developed within the sphere of occupational health services and international health problems. We reviewed publications in the journal International Maritime Health from 2000 to 2010 to establish the coverage of the journal and the scope of research in maritime health. We identified six thematic categories: healthcare access, delivery and integration; telehealth; non-communicable diseases and physical health problems; communicable diseases; psychological functioning and health; and safety-related issues. We describe the research within these themes and report on their publication prominence. We also analyse the research in terms of its geographical focus, the population groups addressed and the research methodologies used. We suggest a broadening of maritime research to include randomised controlled trials, longitudinal studies and more qualitative research; more research addressing the context for non-European seafarers; and research on seafarers spouses and family supports and obligations. We also recommend more research on psychosocial and cultural issues and on telehealth, as well as the development of a stronger systems perspective for promoting maritime health. 相似文献
60.