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61.
62.
Moss RB Rodman D Spencer LT Aitken ML Zeitlin PL Waltz D Milla C Brody AS Clancy JP Ramsey B Hamblett N Heald AE 《Chest》2004,125(2):509-521
STUDY OBJECTIVES: The primary objective was to determine the safety and tolerability of repeated doses of aerosolized adeno-associated serotype 2 vector containing cystic fibrosis transmembrane conductance regulator (CFTR) complementary DNA (cDNA) [tgAAVCF], an adeno-associated virus (AAV) vector encoding the complete human CFTR cDNA. Secondary objectives included evaluation of pulmonary function assessed by spirometry, lung abnormalities by high-resolution CT (HRCT), airway cytokines, vector shedding, serum neutralizing antibody to AAV serotype 2 (AAV2), and gene transfer and expression in a subset of subjects undergoing bronchoscopy with bronchial brushings. DESIGN: Randomized, double-blind, placebo-controlled, phase II trial. SETTING: Eight cystic fibrosis (CF) centers in the United States. SUBJECTS: CF patients with mild lung disease, defined as FEV(1) > or =60% predicted. INTERVENTIONS: Subjects were randomized to inhale three aerosolized doses of 1 x 10(13) deoxyribonuclease-resistant particles of tgAAVCF or matching placebo at 30-day intervals using the Pari LC Plus nebulizer (PARI; Richmond, VA). Measurements and results: Of 42 subjects randomized, 20 subjects received at least one dose of tgAAVCF and 17 subjects received placebo. No difference in the pattern of adverse events or laboratory abnormalities was noted between the two treatment groups. Improvements in induced-sputum interleukin-8 (p = 0.03) and FEV(1) (p = 0.04) were observed at day 14 and day 30, respectively, in the group receiving tgAAVCF when compared to those receiving placebo. No significant differences in HRCT scans were noted. Vector shedding in sputum was observed at low levels up to 90 days after the third dose of vector. All subjects receiving tgAAVCF exhibited an increase (by at least fourfold) in serum AAV2-neutralizing antibodies and detectable levels in BAL fluid from five of six treated subjects undergoing BAL. Gene transfer but not gene expression was detected in a subset of six tgAAVCF subjects who underwent bronchoscopy. CONCLUSIONS: Repeat doses of aerosolized tgAAVCF were safe and well tolerated, and resulted in encouraging trends in improvement in pulmonary function in patients with CF and mild lung disease. 相似文献
63.
Prevalence of malnutrition,obesity and nutritional risk of Australian paediatric inpatients: A national one‐day snapshot
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![点击此处可从《Journal of paediatrics and child health》网站下载免费的PDF全文](/ch/ext_images/free.gif)
64.
Silica inhalation predisposes workers to bacterial infection and impairments in pulmonary defense function. In this study,
we evaluated the effect of pre-exposure to silica on lung defense mechanisms by use of a rat pulmonary Listeria monocytogenes infection model. Male Fischer 344 rats were exposed by inhalation to filtered air or silica (15 mg/m3× 6 h/day × 5 days/wk). After 21 or 59 days of silica exposure, the rats were inoculated intratracheally with 5 × 103
L. monocytogenes. At 0 (noninfected controls), 3, and 7 days after infection, the left lungs were removed, homogenized, and the number of
viable L. monocytogenes was counted after an overnight culture at 37° C. Bronchoalveolar lavage (BAL) was performed on the right lungs. Alveolar
macrophages (AM) were collected, and the AM production of chemiluminescence (CL), an index of reactive oxygen species generation,
was measured. The number of lavagable neutrophils (PMNs) and acellular BAL lactate dehydrogenase (LDH) activity were determined
as indices of inflammation and injury, respectively. Pre-exposure to silica for 59 days caused substantial increases in PMN
number and LDH activity compared with the air controls, whereas silica inhalation for both 21 and 59 days significantly enhanced
the pulmonary clearance of L. monocytogenes compared with air controls. Dramatic elevations were also observed in zymosan- and phorbol myristate acetate (PMA)–stimulated
CL production by lung phagocytes recovered from rats pre-exposed to silica for 59 days. These results demonstrate that short-term
exposure to inhaled silica particles activates lung phagocytes, as evidenced by increases in reactive oxygen species. This
up-regulation in the production of antimicrobial oxidants is likely responsible for the enhancement in pulmonary clearance
of L. monocytogenes observed with short-term silica inhalation.
Accepted for publication: 2 October 2000 相似文献
65.
Machiko R. Tomita Nadine M. Fisher Sujata Nair Dan Ramsey Kimberley Persons 《Physical & occupational therapy in geriatrics》2018,36(1):107-119
Aims: The aim of the study was to determine whether increased physical activities (PA) affect frailty for old women, 75 years and older (OO), compared to 60–74 years old (YO). Methods: This cross-sectional study measured 19 frailty indicators (muscle strength and endurance, balance, gait characteristics, and function), using 46 community-dwelling women. PA were divided into three levels by caloric expenditure per week (<2,000 kcal/week, 2,000–3,999 kcal/week, >4,000 kcal/week). Results: As PA level increased, a gap (=difference) between OO and YO narrowed for step length and function, but for quadriceps strength and endurance, a gap widened. Conclusions: Frailty progresses with aging but older women who engage in a high level of physical activity (>4,000 kcal/week) can increase mobility and functional capacity, but not for muscle strength and endurance. Starting regular resistance training activities early in the aging process is critical to improve or maintain muscle quality to offset age-related frailty. 相似文献
66.
67.
Dal Canto Elisa Remmelzwaal Sharon van Ballegooijen Adriana Johanne Handoko M. Louis Heymans Stephane van Empel Vanessa Paulus Walter J. Nijpels Giel Elders Petra Beulens Joline WJ 《Heart failure reviews》2022,27(1):207-218
Heart Failure Reviews - This study aimed to evaluate the diagnostic performance of echocardiographic markers of heart failure with preserved ejection fraction (HFpEF) and left ventricular diastolic... 相似文献
68.
Genetic engineering of an H-2Dd/Q10b chimeric histocompatibility antigen: purification of soluble protein from transformant cell supernatants
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D H Margulies A L Ramsey L F Boyd J McCluskey 《Proceedings of the National Academy of Sciences of the United States of America》1986,83(14):5252-5256
We have constructed a recombinant class I gene in which 5' sequences of H-2Dd are linked to the 3' half of a Qa subregion gene, Q10b. This hybrid gene would be expected to direct the synthesis of a protein containing the N and C1 domains of H-2Dd covalently linked to the C2 domain of the secreted, nonpolymorphic, Q10b antigen. Following DNA-mediated gene transfer into mouse L cells, transformants were analyzed by radiolabeling and immunoprecipitation. These cells secreted a molecule reactive with anti-H-2Dd monoclonal antibodies that identify epitopes on the N and C1 domains as well as with an anti-Q10 carboxyl-terminal peptide antiserum. The H-2Dd-derived antigen is associated with beta 2-microglobulin and is readily purified in milligram amounts from culture supernatants by immunoaffinity chromatography. 相似文献
69.
Diagnostic accuracy of oropharyngeal cultures in infants and young children with cystic fibrosis. 总被引:3,自引:0,他引:3
M Rosenfeld J Emerson F Accurso D Armstrong R Castile K Grimwood P Hiatt K McCoy S McNamara B Ramsey J Wagener 《Pediatric pulmonology》1999,28(5):321-328
The objective of this study was to assess the diagnostic accuracy of oropharyngeal (OP) cultures relative to simultaneous bronchoalveolar lavage (BAL) cultures in very young children with CF, and to examine the effects of bacterial density, age, and study cohort on diagnostic accuracy. Respiratory culture data were analyzed from three independent, prospective studies involving simultaneous collection of 286 OP and BAL cultures from 141 children with CF <5 years of age. For predicting any growth of Pseudomonas aeruginosa (Pa) from the lower airway in subjects =18 months of age (mean age, 8 +/- 5 months), OP cultures had a sensitivity of 44% (95% CI 14%, 79%), specificity of 95% (90%, 99%), positive predictive value of 44% (14%, 79%), and negative predictive value of 95% (90%, 99%). Diagnostic accuracy was similar for Haemophilus influenzae (Hi). Specificity was significantly lower for Staphylococcus aureus (Sa). Sensitivity for all organisms improved if a positive lower airway culture was defined as >/=10(3) or >/=10(5) cfu/mL. Specificity for Pa declined significantly with increasing age. In children with CF <5 years of age, the specificity and negative predictive value of OP cultures for Pa are high, while the sensitivity and positive predictive value are poor. Thus, in this age range, a negative throat culture is helpful in "ruling out" lower airway infection with Pa. However, a positive culture does not reliably "rule in" the presence of Pa in the lower respiratory tract. These findings may have implications for study design and interpretation as well as clinical management of young children with CF. 相似文献
70.