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991.
Pahar B Cantu MA Zhao W Kuroda MJ Veazey RS Montefiori DC Clements JD Aye PP Lackner AA Lovgren-Bengtsson K Sestak K 《Vaccine》2006,24(47-48):6839-6849
The difficulty in developing an effective vaccine to contain the HIV/AIDS epidemic coupled with the fact that primary HIV-1 infection typically occurs via mucosal sites has increased emphasis on vaccine approaches that protect at mucosal surfaces. In this study we employed HIV and simian-HIV (SHIV)-derived T helper (Th) and cytotoxic T lymphocyte (CTL) single epitopes incorporated into immuno-stimulating complexes (ISCOM) as a candidate immunogens. Immunized rhesus macaques (Macaca mulatta) were challenged with CCR5-tropic SHIV(SF162p4). On the day of challenge, low levels of virus-neutralizing antibodies (Ab) and CTLs were detected in ISCOM-immunized macaques. Greater than 10(5) viral RNA copies per ml of plasma in 2/5 immunized and 3/4 control macaques were detected within 3 weeks post-challenge. Depletion of CD4+ T cells from gut-associated lymphoid tissues (GALT) was observed by post-challenge day (PCD) 14 in all macaques regardless immunization. Nonetheless, lower viral loads and relatively better preservation of peripheral CD4+ T cells following the SHIV infection was observed in ISCOM-immunized macaques. We predict that if coadministered with additional epitopes and/or more efficacious mucosal delivery system or route, HIV/SIV-derived peptide vaccines may have potential to elicit heterologous protection. 相似文献
992.
All medicines have adverse effects as well as benefits. The aim of pharmacovigilance is to protect public health by monitoring medicines to identify and evaluate issues and ensure that the overall benefits outweigh the potential risks. The tools and processes used in pharmacovigilance are continually evolving. Increasingly sophisticated tools are being designed to evaluate safety data from clinical trials to enhance the likelihood of detecting safety signals ahead of product registration. Methods include integration of safety data throughout development, meta-analytical techniques, quantitative and qualitative methods for evaluation of adverse event data and graphical tools to explore laboratory and biometric data. Electronic data capture facilitates monitoring of ongoing studies so that it is possible to promptly identify potential issues and manage patient safety. In addition, GSK employs a number of proactive methods for post-marketing signal detection and knowledge management using state-of-the-art statistical and analytical tools. Using these tools, together with safety data collected through pharmacoepidemiologic studies, literature and spontaneous reporting, potential adverse drug reactions can be better identified in marketed products. In summary, the information outlined in this paper provides a valuable benchmark for risk management and pharmacovigilance in pharmaceutical development. 相似文献
993.
994.
Aleksander Zuch Karol Buluk Maria Rudobielska Walentyna Zwierzowa 《European journal of pediatrics》1972,112(2):142-152
Actual and potential fibrin-stabilizing factor (FSF) activity in the blood plasma of children in various are groups and in adults was estimated. Differences in blood plasma activities regarding desmofibrin formation were revealed, which depended upon the changes in enzyme concentration varying with age and upon the changes in thiol group concentration.Investigation partly subsidized by Department VI of the Polish Academy of Sciences. 相似文献
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997.
It is estimated that 25 per cent of pregnancies in the United States are complicated by some form of substance abuse. Cocaine use has been on the increase. In some parts of the country 10 per cent of all deliveries are made problematic by maternal cocaine addiction.
This report is based on a comparison of cry characteristics of neonates born to drug-using mothers who also used cocaine and those born to women who were not drug-users. All infants were full term.
Pain cries were elicited by snaps with a rubber band against the foot, on two occasions during the first 48 hours of life. Cry data were processed at Kay Elemetrics via DSP Sona-Graph 5500.
Fundamental frequencies [F#dg] of cries of newborn infants whose mothers used drugs including cocaine, show wide individual differences, ranging between 340 and 700 Hz on the first occasion, with a mean of 480 Hz. This exceeds values for normal infants in the same nursery as well as mean Hz's for normal infants reported by Thoden and Koivisto [330-410 Hz] and Michelsson [330-420 Hz] [Thoden & Koivisto, 1980; Michelsson, 1980]. F#dg's shift downward on the second occasion, a reduction not characteristic for normal infants in the same nursery and therefore not likely to be due to regression toward the mean. Cry durations of newborns exposed to drugs in utero are short. Cries show numerous pathological signs not attributable to poor prenatal care, low birth weight or prematurity. Examples of sonographs from the drug-exposed group are presented. It is concluded that further study of the effects of prenatal drug exposure on the neonatal cry is justified. 相似文献
This report is based on a comparison of cry characteristics of neonates born to drug-using mothers who also used cocaine and those born to women who were not drug-users. All infants were full term.
Pain cries were elicited by snaps with a rubber band against the foot, on two occasions during the first 48 hours of life. Cry data were processed at Kay Elemetrics via DSP Sona-Graph 5500.
Fundamental frequencies [F#dg] of cries of newborn infants whose mothers used drugs including cocaine, show wide individual differences, ranging between 340 and 700 Hz on the first occasion, with a mean of 480 Hz. This exceeds values for normal infants in the same nursery as well as mean Hz's for normal infants reported by Thoden and Koivisto [330-410 Hz] and Michelsson [330-420 Hz] [Thoden & Koivisto, 1980; Michelsson, 1980]. F#dg's shift downward on the second occasion, a reduction not characteristic for normal infants in the same nursery and therefore not likely to be due to regression toward the mean. Cry durations of newborns exposed to drugs in utero are short. Cries show numerous pathological signs not attributable to poor prenatal care, low birth weight or prematurity. Examples of sonographs from the drug-exposed group are presented. It is concluded that further study of the effects of prenatal drug exposure on the neonatal cry is justified. 相似文献
998.
E J Seifter P A Bunn M H Cohen R W Makuch N R Dunnick N Javadpour H Bensimon J L Eddy J D Minna D C Ihde 《Journal of clinical oncology》1986,4(9):1365-1373
We administered combination chemotherapy with cyclophosphamide, doxorubicin, and cisplatin to 25 previously untreated patients with metastatic prostate cancer in order to assess the efficacy of chemotherapy before any hormonal manipulation. Hormonal therapy was administered only after progression of disease to chemotherapy. All 25 patients were followed until time of death and all were able to receive hormonal therapy. We did not find substantially improved response rates when combination chemotherapy was applied before endocrine treatment since the 33% objective response rate to chemotherapy was only minimally higher than the response in our patients who had failed hormonal therapy and then received identical or similar chemotherapy. Furthermore, the introduction of intensive combination chemotherapy before hormonal therapy in our study did not result in any striking improvement in overall survival compared with patients who received initial hormonal therapy in many other studies. Responses to chemotherapy were not attributable to suppression of serum testosterone since all 12 patients with partial response (PR) or stable disease (SD) and four of seven patients with no response (NR) had normal testosterone levels at the time of response assessment. The initial use of chemotherapy did not adversely affect the expected high percentage of objective responses (68%) to subsequent hormonal manipulation. The frequency, duration, and quality of responses to hormonal therapy exceeded the responses to chemotherapy. The disappointing responses to chemotherapy reflect the very modest efficacy of even aggressively delivered cytotoxic agents. 相似文献
999.
D D Von Hoff J Casper E Bradley J M Trent A Hodach C Reichert R Makuch A Altman 《Cancer research》1980,40(10):3591-3597
An in vitro soft agar technique was used in an attempt to culture neuroblastoma cells from 71 bone marrow, 3 lymph node, and 2 solid tumor specimens from 18 patients with neuroblastoma. One-half of each specimen was sent for routine pathology studies and one-half was cultured in the soft agar system. Colonies appeared within 10 days in histologically positive bone marrows. Light microscopy, electron microscopy, catecholamine secretion, and karyology provided evidence that the colonies were composed of neuroblastoma cells. There were 38 instances in which histological study of the specimen demonstrated neuroblastoma cells. The soft agar system showed colony growth in 30 of these samples (79%). There were a total of 38 specimens that were histologically negative for neuroblastoma. Thirty of these 38 specimens showed no growth in the stem cell assay. Eight histologically negative specimens from 6 patients formed colonies in the soft agar system. Five of these 6 patients showed tumor histologically on prior or subsequent marrow examinations. In addition to a significant correlation between histological and soft agar culture results (p < 0.001), there exists a highly significant positive correlation between the number of colonies per plate and the histological status of the specimen (p < 0.005). Serial marrow samples were cultured on 7 patients. There appears to be an association between the number of colonies that develop in the plate and the clinical course and prognosis of the patient. Decreasing plating efficiencies (number of colonies per number of cells plated) correlated with tumor response. Increasing plating efficiencies indicated tumor relapse. A plating efficiency of greater than or equal to 0.1% portended a particularly poor prognosis. Neuroblastoma grows well in this soft agar culture system. This excellent growth provides a good model for both clinical and basic science studies of neuroblastoma. 相似文献
1000.