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951.
Nigel S. Cook Ian D. Chapman 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》1993,7(Z3):555-563
Potassium channel opener's (KCOs) were originally thought of as nonselective smooth muscle relaxants. However, recent investigations in animal models of both peripheral vascular disease (PVD) and asthma have revealed interesting effects of these drugs at unexpectedly low doses. Hemodynamically, KCOs are interesting in PVD since they have little effect on blood supply to normally perfused skeletal muscle, but enhance perfusion to chronically ligated ischemic tissue. In animal PVD models, SDZ PCO-400 and cromakalim have been shown to improve recovery of muscle energy stores from ischemia or to preserve performance under conditions of ischemic contracture. Beneficial effects in rat PVD models were manifest at doses below those affecting systemic blood pressure and may be attributable to a selective dilatation of collateral vessels. With regard to the airways, the apparent efficacy of KCOs as antiasthmatic drugs seems not to be attributable solely to their bronchodilator activity. Although KCOs elicit no antiinflammatory effect in animal models, studies with SDZ PCO-400 in guinea pigs sensitized to antigen or treated with immune complexes have revealed that expression of airway hyperreactivity is significantly inhibited at drug doses exhibiting only modest bronchodilator activity. At least part of this action can be attributed to inhibition at the level of neural innervation of the airways, possibly through attenuation of nonadrenergic noncholinergic (NANC) transmission. Thus, based on results generated in animal models of asthma and PVD, clinical evaluation of the KCOs in these indications would seem warranted, with the hope that (due to their selective actions) beneficial therapeutic effects can be achieved at doses devoid of unwanted systemic actions. 相似文献
952.
Discrimination and abuse in internal medicine residency 总被引:3,自引:0,他引:3
Cornelia H. M. vanIneveld MD FRCPC Dr. Deborah J. Cook MD FRCPC Sheri-Lynn C. Kane MD FRCPC Derek King B Math 《Journal of general internal medicine》1996,11(7):401-405
OBJECTIVE: To survey the extent to which internal medicine housestaff experience abuse and discrimination in their training.
DESIGN: Through a literature review and resident focus groups, we developed a self-administered questionnaire. In this cross-sectional
survey, respondents were asked to record the frequency with which they experienced and witnessed different types of abuse
and discrimination during residency training, using a 7-point Likert scale.
PARTICIPANTS: Internal medicine housestaff in Canada.
MEASUREMENTS AND MAIN RESULTS: Of 543 residents in 13 programs participating (84% response rate), 35% were female. Psychological abuse, as reported by attending
physicians (68%), patients (79%), and nurses or other health workers (77%), was widespread. Female residents experienced gender
discrimination by attending physicians (70%), patients (88%), and nurses (71%); rates for males were 23%, 38%, and 35%, respectively.
Females reported being sexually harassed more often than males, by attending physicians (35% vs 4%,p<.01), peers (30% vs 6%,p<.01), and patients (56% vs 18%,p<.01). Physical assault by patients was experienced by 40% of residents. Half of the residents surveyed reported racial discrimination
and homophobic remarks in the workplace, perpetrated by all groups of health professionals.
CONCLUSIONS: Psychological abuse, gender discrimination, sexual harassment, physical abuse, homophobia, and racial discrimination are
prevalent problems during residency training. Housestaff, medical educators, allied health workers, and the public need to
work together to address these problems in the training environment.
Dr. Cook is a Career Scientist with the Ontario Ministry of Health.
For a complete listing, see Appendix A.
This study was supported by the Royal College of Physicians and Surgeons of Canada. 相似文献
953.
954.
The amino acid sequences of human inhibin alpha-, beta A- and beta B-subunits were analyzed for hydrophilicity and chain flexibility to predict regions that are on the surface of the subunits and, therefore, are potential antigenic sites. Based on these analyses, a total of nine peptides were synthesized, and rabbit antisera against the peptides were prepared. Peptides of the N-terminus (residues 1-16 and 13-24) and region 109-123 of the alpha-subunit produced high titer antibodies. Regions 69-79 and 93-105 of the beta A-subunit and region 93-104 of the beta B-subunit were also immunogenic. Immunoblotting of an inhibin preparation with anti-alpha-peptide antiserum revealed that a 32K band (inhibin) and an 18K band (alpha-subunit) were stained. Immunoblotting with anti-beta-peptide antiserum detected a 32K band (inhibin), a 24K band (activin), and a 14K band (beta-subunit). Injection (iv) of these antisera into rats induced dramatic elevation of serum FSH in 6-12 h and suggested immunoneutralization of endogenous inhibin. RIAs for each subunit were developed using radioiodinated peptides as tracers. Competition binding assays indicated crossreactivity with human follicular fluid, semen, serum, plasma, and crude inhibin preparations. Parallel dilution curves were obtained. Antisera against beta A- and beta B-subunit peptide cross-reacted with each other. In immunocytochemical studies, these antisera were used in conjunction with gold-labeled goat antirabbit immunoglobulin G to localize inhibin in cells of the rat testis. Specific staining of inhibin was localized within the Sertoli cells of some tubules in adult rat testis. Positive staining could be blocked by preadsorbing the sera with the appropriate synthetic peptide. These results suggest that antibodies against synthetic inhibin peptides are useful in elucidating the roles of inhibin and activin. 相似文献
955.
Sheen AJ Irlam J Kirillova N Guest RD Sherlock DJ Hawkins RE Gilham DE 《Diseases of the colon and rectum》2003,46(6):793-804
PURPOSE: The overall aim of this study was to develop a novel treatment for colorectal cancer based on the use of gene therapy. Genetic modification of T lymphocytes has been used to specifically target and kill tumor cell lines directly. To test the efficacy of this method with clinically relevant materials, this study investigated the potential of T lymphocytes derived from patients with advanced colorectal disease to target autologous primary tumor material.
METHODS: T lymphocytes isolated preoperatively were modified genetically with recombinant retroviruses encoding CD3-based chimeric immune receptors and were tested for functional activity against freshly isolated autologous tumor cells harvested from hepatic colorectal metastases.
RESULTS: Patient-derived T cells were successfully transduced, and chimeric immune receptor expression was confirmed. Carcinoembryonic antigen expression on freshly isolated colorectal tumor cells was also demonstrated by molecular and immunohistochemical techniques. T cells expressing the anticarcinoembryonic antigen receptor were specifically activated by coculture with disaggregated or intact, diced tumor, whereas control non-carcinoembryonic antigen-targeted T-cell populations failed to activate.
CONCLUSIONS: These results indicate that gene-targeted primary T lymphocytes depict specific functional activity against autologous colorectal tumor cells. This evidence indicates that chimeric immune receptor-expressing T cells may be able to circumvent the mechanisms used by tumor cells to avoid immune cell activity in vivo. This study emphasizes the potential of this approach as a therapy for carcinoembryonic antigen-expressing primary colorectal tumor and its metastases. 相似文献
956.
Wang A Jaggers J Ungerleider RM Lim CS Ryan T 《The Journal of heart valve disease》2003,12(2):202-208
BACKGROUND AND AIM OF THE STUDY: The pulmonary autograft, or Ross procedure, has theoretical hemodynamic benefits over other aortic valve replacements. The hemodynamic performance of the pulmonary autograft and pulmonary homograft components of this procedure have not been well defined. METHODS: Twenty patients with pulmonary autograft replacement of the aortic valve and six with aortic homografts underwent exercise echocardiography with assessment of exercise duration, left ventricular dimensions, mass, and function. Hemodynamics at rest and maximal exercise, including Doppler gradients and effective orifice area (EOA), were measured across the pulmonary autograft and aortic homograft valves. Doppler gradients across the pulmonary homograft valves were compared to native pulmonary valve gradients at rest and maximal exercise. RESULTS: Both groups of patients had excellent self-reported and measured exercise capacity. In comparison to the aortic homograft, the pulmonary autograft had lower peak Doppler gradients across the neoaortic valve at rest (5 +/- 2 versus 11 +/- 4 mmHg; p = 0.027) and maximal exercise (10 +/- 5 versus 15 +/- 5 mmHg; p = 0.003) and larger indexed EOA. However, the Ross procedure patients had higher gradients across the pulmonary homograft both at rest (14 +/- 10 versus 3 +/- 1 mmHg; p < 0.001) and maximal exercise (25 +/- 22 versus 5 +/- 4 mmHg; p = 0.004). Two patients in the Ross procedure group had significant pulmonary homograft stenosis in short- or mid-term follow up. CONCLUSION: In comparison to aortic homograft replacement of the aortic valve, pulmonary autograft replacement has superior hemodynamics at rest and during exercise. However, the pulmonary homograft replacement may develop hemodynamically significant stenosis after the Ross procedure. 相似文献
957.
c-myc and bcl-2 modulate p53 function by altering p53 subcellular trafficking during the cell cycle. 总被引:17,自引:1,他引:17
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J J Ryan E Prochownik C A Gottlieb I J Apel R Merino G Nu?ez M F Clarke 《Proceedings of the National Academy of Sciences of the United States of America》1994,91(13):5878-5882
We have studied the ability of c-myc and bcl-2 oncogenes to modulate p53 function. Our studies show that coincident expression of human Bcl-2 protein with p53 prolongs survival of murine erythroleukemia cells. This effect was associated with a loss of the G1 specificity of p53-mediated cell cycle arrest. Furthermore, we found that the c-myc and bcl-2 genes cooperate to inhibit p53 functions. Coexpression of bcl-2 and c-myc can totally overcome p53-induced apoptosis and cell cycle arrest by altering the subcellular trafficking of p53 during the cell cycle: the p53 remains in the cytoplasm of the cotransfected cells during a critical period in G1. This finding suggests a mechanism by which normal hematopoietic progenitors can survive and proliferate despite p53 expression and by which the inappropriate expression of bcl-2 and c-myc can cooperate in transformation. 相似文献
958.
Long-term follow-up after transplantation of insulin-producing pancreatic islets into patients with Type 1 (insulin-dependent) diabetes mellitus 总被引:7,自引:0,他引:7
Summary Purified human islets and a kidney from the same donor were transplanted into four patients with Type 1 (insulin-dependent) diabetes mellitus. Two of the patients received additional islets that were isolated from multiple donors, cryopreserved, and stored in a tissue bank. The islets were embolized into the liver via the portal vein. Immunosuppression was induced with antilymphocyte globulin and maintained with azathioprine, prednisone and cyclosporine. In the first two patients, fasting serum C-peptide rose to levels of 0.5–2.0 ng/ml during the first 4–8 weeks and mixed meal feeding elicited increases to 2–3 ng/ml. C-peptide secretion persisted for 8 months, but at progressively lower levels and insulin therapy could not be withdrawn. In the next two patients who received cryopreserved islets in addition to fresh islets, serum C-peptide levels (fasting/post-meal) rose to 4–7 ng/ml and serum glucose was more stable, allowing withdrawal of insulin therapy after 69 days in one patient, and reduced insulin doses in the other. The insulin-independent patient has maintained normal fasting glucose, glycosylated haemoglobin, and oral glucose tolerance at 1 year following cessation of daily insulin therapy. Episodes of renal graft rejection occurred in three patients, including the insulin-independent patient. High-dose steroid therapy reversed the rejection in all instances, with apparent preservation of C-peptide secretion. These data show that transplantation of purified freshly-prepared and cryopreserved islets into Type 1 diabetic patients results in prolonged insulin secretion, and that sufficient function could be provided in one patient to sustain euglycaemia in the absence of insulin therapy at 1 year of follow-up. 相似文献
959.
Carlos Collet Yosuke Miyazaki Nicola Ryan Taku Asano Erhan Tenekecioglu Jeroen Sonck Daniele Andreini Manel Sabate Salvatore Brugaletta Rodney H. Stables Antonio Bartorelli Robbert J. de Winter Yuki Katagiri Ply Chichareon Giovanni Luigi De Maria Pannipa Suwannasom Rafael Cavalcante Hans Jonker Patrick W. Serruys 《Journal of the American College of Cardiology》2018,71(24):2756-2769
Background
The functional SYNTAX score (FSS) has been shown to improve the discrimination for major adverse cardiac events compared with the anatomic SYNTAX score (SS) while reducing interobserver variability. However, evidence supporting the noninvasive FSS in patients with multivessel coronary artery disease (CAD) is scarce.Objectives
The purpose of this study was to assess the feasibility of and validate the noninvasive FSS derived from coronary computed tomography angiography (CTA) with fractional flow reserve (FFRCT) in patients with 3-vessel CAD.Methods
The CTA-SS was calculated in patients with 3-vessel CAD included in the SYNTAX II (SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery II) study. The noninvasive FSS was determined by including only ischemia-producing lesions (FFRCT ≤0.80). SS derived from different imaging modalities were compared using the Bland-Altman and Passing-Bablok method, and the agreement on the SS tertiles was investigated with Cohen’s Kappa. The risk reclassification was compared between the noninvasive and invasive physiological assessment, and the diagnostic accuracy of FFRCT was assessed by the area under the receiver-operating characteristic curve using instantaneous wave-free ratio as a reference.Results
The CTA-SS was feasible in 86% of patients (66 of 77), whereas the noninvasive FSS was feasible in 80% (53 of 66). The anatomic SS was overestimated by CTA compared with conventional angiography (27.6 ± 6.4 vs. 25.3 ± 6.9; p < 0.0001) whereas the calculation of the FSS yielded similar results between the noninvasive and invasive imaging modalities (21.6 ± 7.8 vs. 21.2 ± 8.8; p = 0.589). The noninvasive FSS reclassified 30% of patients from the high- and intermediate-SS tertiles to the low-risk tertile, whereas invasive FSS reclassified 23% of patients from the high- and intermediate-SS tertiles to the low-risk tertile. The agreement on the classic SS tertiles based on Kappa statistics was slight for the anatomic SS (Kappa = 0.19) and fair for the FSS (Kappa = 0.32). The diagnostic accuracy of FFRCT to detect functional significant stenosis based on an instantaneous wave-free ratio ≤0.89 revealed an area under the receiver-operating characteristics curve of 0.85 (95% CI: 0.79 to 0.90) with a sensitivity of 95% (95% CI: 89% to 98%), specificity of 61% (95% CI: 48% to 73%), positive predictive value of 81% (95% CI: 76% to 86%), and negative predictive value of 87% (95% CI: 74% to 94%).Conclusions
Calculation of the noninvasive FSS is feasible and yielded similar results to those obtained with invasive pressure-wire assessment. The agreement on the SYNTAX score tertile classification improved with the inclusion of the functional component from slight to fair agreement. FFRCT has good accuracy in detecting functionally significant lesions in patients with 3-vessel CAD. (A Trial to Evaluate a New Strategy in the Functional Assessment of 3-Vessel Disease Using SYNTAX II Score in Patients Treated With PCI; NCT02015832) 相似文献960.
Approximately 6% of paediatric patients with precursor B-cell acute lymphoblastic leukaemia (B-ALL) harbour a rearrangement involving the gene regions of PBX1 (1q23) and E2A (19p13.3) which is visualized cytogenetically either as a der(19)t(1;19)(q23;p13.3) or the less common balanced t(1;19)(q23;p13.3). Unfortunately, no commercial dual-colour, double fusion fluorescence in situ hybridization (D-FISH) strategies are available to detect this recurrent anomaly. Therefore, we have created a D-FISH assay to detect these translocations and monitor minimal residual disease. This probe set was created using four bacterial artificial chromosomes (BACs) corresponding to the PBX1 gene region at 1q23 and four BACs corresponding to the E2A gene region at 19p13.3. We analysed 30 negative bone marrow controls and 20 diagnostic and post-treatment specimens from 13 paediatric B-ALL patients with a cytogenetically defined 1;19 translocation. Once unblinded, the results demonstrated that our D-FISH method effectively identified all diagnostic samples as abnormal and identified disease in four post-treatment samples that were previously considered to be normal by conventional cytogenetic analysis. The development of this FISH strategy for the detection of der(19)t(1;19)(q23;p13.3) and t(1;19)(q23;p13.3) proved to be an effective technique, allowing both the detection of disease in diagnostic samples and in post-treatment samples. 相似文献