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21.
Nazanin Zounemat Kermani Mansoor Saqi Paul Agapow Stelios Pavlidis Chihhsi Kuo Kai Sen Tan Sharon Mumby Kai Sun Matthew Loza Frederic Baribaud Ana R. Sousa John Riley Asa M. Wheelock Craig E. Wheelock Bertrand De Meulder Jim Schofield Stephany Sánchez-Ovando Jodie Louise Simpson Katherine Joanne Baines Peter A. Wark Charles Auffray Sven-Erik Dahlen Peter J. Sterk Ratko Djukanovic Ian M. Adcock Yi-ke Guo Kian Fan Chung U-BIOPRED Project Team 《Allergy》2021,76(1):380-383
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Landon Wark David Novak Nelly Sabbaghian Lilian Amrein Jaganmohan R. Jangamreddy Mary Cheang Carly Pouchet Raquel Aloyz William D. Foulkes Sabine Mai Marc Tischkowitz 《Genes, chromosomes & cancer》2013,52(5):480-494
PALB2/FANCN is a BRCA1‐ and BRCA2‐interacting Fanconi Anemia (FA) protein crucial for key BRCA2 genome caretaker functions. Heterozygous germline mutations in PALB2 predispose to breast cancer and biallelic mutations cause FA. FA proteins play a critical role in the telomere maintenance pathway, with telomeric shortening observed in FA cells. Less is known about telomere maintenance in the heterozygous state. Here, we investigate the roles of PALB2 heterozygous mutations in genomic instability, an important carcinogenesis precursor. Patient‐derived lymphoblastoid (LCL) and fibroblast (FCL) cell lines with monoallelic truncating PALB2 mutations were investigated using a combination of molecular imaging techniques including centromeric FISH, telomeric Q‐FISH and spectral karyotyping (SKY). Mitomycin C and Cisplatin sensitivity was assayed via cellular metabolism of WST‐1. The PALB2 c.229delT FCL showed increases in telomere counts associated with increased mean intensity compared with two wild‐type FCLs generated from first‐degree relatives (P =1.04E‐10 and P =9.68E‐15) and it showed evidence of chromosomal rearrangements. Significant differences in centromere distribution were observed in one of three PALB2 heterozygous FCLs analyzed when compared with PALB2 wild‐type, BRCA1 and BRCA2 heterozygous FCLs. No significant consistently increased sensitivity to Mitomycin C or Cisplatin was observed in LCLs. Our results are suggestive of an altered centromere distribution profile and a telomere instability phenotype. Together, these may indicate critical nuclear organization defects associated with the predisposition to transformation and early stage development of PALB2‐related cancers. © 2013 Wiley Periodicals, Inc. 相似文献
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Muscle beta-actinin and serum albumin of the chicken are indistinguishable by physicochemical and immunological criteria
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C W Heizman G Müller E Jenny K J Wilson F Landon A Olomucki 《Proceedings of the National Academy of Sciences of the United States of America》1981,78(1):74-77
Chicken muscle beta-actinin is considered to be one of the "true" myofibrillar components due to its specific binding to isolated myofibrils. Surprisingly, the direct comparison of this muscle protein with serum albumin, both isolated from chicken, showed that they behaved identically under several electrophoretic conditions. Furthermore, immunoreplica gels and double-immunodiffusion tests with antibodies prepared against beta-actinin established the serological identity of both proteins. No significant differences were found by circular dichroic spectroscopy or in amino acid composition. In addition, the amino-terminal sequences of both proteins were identical (H2N-Asp-Ala-Glu-His-Lys-Ser-Glu-Ile-Ala-His-Arg-Tyr-Asn-Asp-Leu-). Combined, these results strongly indicate that muscle beta-actinin and serum albumin are similar, if not identical. 相似文献
25.
Specialty training and specialization among physicians who treat HIV/AIDS in the United States
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Landon BE Wilson IB Wenger NS Cohn SE Fichtenbaum CJ Bozzette SA Shapiro MF Cleary PD 《Journal of general internal medicine》2002,17(1):12-22
OBJECTIVE: To assess the association of specialty training and experience in the care of HIV disease with HIV-specific knowledge, referral patterns, and HIV-related education activities. DESIGN: Cross-sectional survey. SETTING: The United States. PARTICIPANTS: Physicians caring for patients in the HIV Costs and Service Utilization Study, a study of a probability sample of HIV-infected individuals in the United States. MEASUREMENTS AND MAIN RESULTS: Measures included physicians' reports of specialty training and HIV caseload, scores on an HIV-specific knowledge test, referral patterns, and attendance rates at HIV-related educational activities. Approximately 72% (379) of the eligible physicians completed a survey. Of these, 152 (40%) had infectious disease (ID) training, and 213 (56%) were generalists; 4% of ID-trained physicians and 37% of generalist physicians did not consider themselves HIV experts. The median current caseloads were 150 and 200 patients for ID experts and generalist experts, respectively. In contrast, the median caseload for non-expert generalists was 5. Mean scores on the knowledge scale were similar for ID and generalist experts (9.0 items correct out of 11 vs 8.5; P=not significant), but lower for generalist non-experts (6.5 items correct; P <.01). Experts had attended more local and national HIV meetings than non-experts (9.3 vs 2.7; P <.01, and 2.3 vs.40; P <.01, respectively) in the past year. Fewer ID experts ever referred than generalist experts (13.0% vs 27.3%; P=.01). In multivariable models that included specialty training and caseload, physicians with caseloads of 20 to 49 and >50 were more likely to have a high knowledge score (defined as 80% or more correct, odds ratio [OR], 2.8; P=.04 and OR, 5.7; P <.001, respectively), and the effect of specialty was attenuated (OR, 2.7; P=.02 decreased from OR, 7.8; P <.001 in a model without caseload). In the models predicting referral practices, both experience (OR,.25; P <.01 and OR,.17; P <.01 for caseloads of 20 to 49 and >50, respectively) and specialty (OR,.19; P <.01 and OR,.09; P <.01 for generalist and ID experts, respectively) were significant. CONCLUSIONS: In a national sample of physicians, HIV-specific knowledge was more strongly associated with HIV caseload than with specialty training. In addition, although referral practices were related to both experience and specialty, generalist experts and ID physicians reported similar behaviors. This suggests that generalist physicians, through clinical experience and self-education, can develop specialized knowledge in HIV care. 相似文献
26.
In a canine pneumonia model of exchange transfusion,altering the age but not the volume of older red blood cells markedly alters outcome
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Stripping of cytoplasm from circulating megakaryocytes (MKs) in the pulmonary capillary bed implicates the lungs as an important site for platelet production in normal physiology. The placenta has been proposed as an alternative location for intrauterine platelet production as fetal lungs are essentially non-functioning. To investigate this further, circulating MKs from an umbilical artery and umbilical vein of 10 human placentae were isolated using a modified whole blood filtration technique. Pretreatment of blood, which may be deleterious to MKs, was not required. Following May Grunwald Giemsa staining of filters, MKs were identified by their morphology and classified into 4 types based on subjective assessment of the amount of cytoplasm present. Blood from umbilical arteries and veins contained a mean of 37.2 MKs/0.5 ml (median 37.0; range 17-80) and 23.9 MKs/0.5 ml (median 18.5; range 5-67) respectively (p < 0.01). 43% of arterial MKs and 14% of venous MKs possessed copious cytoplasm (p < 0.01). These results demonstrate a significant reduction of MK numbers across the placenta. Removal of MK cytoplasm at this site is consistent with the hypothesis that the placenta functions as a platelet forming organ during intrauterine life, the lungs taking over this role after birth. 相似文献
28.
Mark B. Landon Madeline Murguia Rice Michael W. Varner Brian M. Casey Uma M. Reddy Ronald J. Wapner Dwight J. Rouse Joseph R. Biggio Jr. John M. Thorp Edward K. Chien George Saade Alan M. Peaceman Sean C. Blackwell J. Peter VanDorsten 《Diabetes care》2015,38(3):445-452
OBJECTIVETo evaluate whether treatment of mild gestational diabetes mellitus (GDM) confers sustained offspring health benefits, including a lower frequency of obesity.RESULTSFive hundred of 905 eligible offspring (55%) were enrolled. Maternal baseline characteristics were similar between the follow-up treated and untreated groups. The frequencies of BMI ≥95th (20.8% and 22.9%) and 85th (32.6% and 38.6%) percentiles were not significantly different in treated versus untreated offspring (P = 0.69 and P = 0.26). No associations were observed for BMI z score, log waist circumference, log triglycerides, HDL cholesterol, blood pressure, or log HOMA-estimated insulin resistance (HOMA-IR). The effect of treatment was different by sex for fasting glucose and log HOMA-IR (P for interaction = 0.002 and 0.02, respectively) but not by age-group (5–6 and 7–10 years) for any outcomes. Female offspring of treated women had significantly lower fasting glucose levels.CONCLUSIONSAlthough treatment for mild GDM has been associated with neonatal benefits, no reduction in childhood obesity or metabolic dysfunction in the offspring of treated women was found. However, only female offspring of women treated for mild GDM had lower fasting glucose. 相似文献
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