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11.
12.
Nelson Rhodes Theresa DSouza Christine D. Foster Yael Ziv David G. Kirsch Yosef Shiloh Michael B. Kastan Peter H. Reinhart Tona M. Gilmer 《Genes & development》1998,12(23):3686-3692
Similarities exist between the progressive cerebellar ataxia in ataxia telangiectasia (AT) patients and a number of neurodegenerative diseases in both mouse and man involving specific mutations in ion channels and/or ion channel activity. These relationships led us to investigate the possibility of defective ion channel activity in AT cells. We examined changes in the membrane potential of AT fibroblasts in response to extracellular cation addition and found that the ability of AT fibroblasts to depolarize in response to increasing concentrations of extracellular K+ is significantly reduced when compared with control fibroblasts. Electrophysiological measurements performed with a number of AT cell lines, as well as two matched sets of primary AT fibroblast cultures, reveal that outward rectifier K+ currents are largely absent in AT fibroblasts in comparison with control cells. These K+ current defects can be corrected in AT fibroblasts transfected with the full-length ATM cDNA. These data implicate, for the first time, a role for ATM in the regulation of K+ channel activity and membrane potential. 相似文献
13.
Blumenfeld Zeev; Dirnfeld Martha; Gonen Yael; Abramovici Haim 《Human reproduction (Oxford, England)》1994,9(2):209-213
To investigate the effect of co-treatment with growth hormone(GH) for ovulation induction with human menopausal gonadotrophins(HMG) on conception, we compared the pregnancy rate and responseto co-treatment with GH versus HMG/human chorionic gonadotrophin(HCG) alone in a prospective, randomized, cross-over protocolof volation induction for either in-vivo or in-vitro fertilization(IVF). The main outcome measures were the amount of gonadotrophinused and conception. Co-treatment with GH was associated witha reduction of 30% in gonadotrophin requirement. In 24 clonidinenegative patients 14 pregnancies were achieved (58.3%) eitherin the GH/HMG/HCG cycle or in the succeeding one. GH co-treatmentdid not generate any pregnancy in eight clonidine positive patients.We conclude that growth hormone may increase the pregnancy ratewhen combined with HMG/HCG for ovulation induction, not onlyin the co-treatment cycle but also in the succeeding one. Thebeneficial, synergistic effect of GH co-treatment was detectedin clonidine negative but not in clonidine positive infertilepatients. 相似文献
14.
The complete sequence of the coding region of the ATM gene reveals similarity to cell cycle regulators in different species 总被引:30,自引:3,他引:30
Savitsky Kinneret; Sfez Sharon; Tagle Danilo A.; Ziv Yael; Sartiel Adam; Collins Francis S.; Shiloh Yosef; Rotman Gallt 《Human molecular genetics》1995,4(11):2025-2032
Ataxia-telangiectasia (A-T) is an autosomal recessive disorderinvolving cerebellar degeneration, immunodeficiency, radiationsensitivity, and cancer predisposition. A-T heterozygotes aremoderately cancer prone. The A-T gene, designated ATM, was recentlyidentified in our laboratory by positional cloning, and a partialcDNA clone was found to encode a polypeptide with a PI-3 kinasedomain. We report here the molecular cloning of a cDNA contigspanning the complete open reading frame of the ATM gene. Thepredicted protein of 3056 amino acids shows significant sequencesimilarities to several large proteins in yeast, Drosophilaand mammals, all of which share the PI-3 kinase domain. Manyof these proteins are involved in the detection of DNA damageand the control of cell cycle progression. Mutations in theirgenes confer a variety of phenotypes with features similar tothose observed in human A-T cells. The complete sequence ofthe ATM gene product provides useful clues to the function ofthis protein, and furthers understanding of the pleiotropicnature of the A-T mutations. 相似文献
15.
Goldberg I Gilburd B Kravitz MS Kivity S Chaim BB Klein T Schiffenbauer Y Trubniykovr E Brenner S Shoenfeld Y 《Clinical & developmental immunology》2005,12(1):85-90
Background: There are several mechanisms to describe allergic drug
reactions yet the methods to diagnose them are limited.
Objective: To compare several conventional clinical and laboratory
methods to diagnose skin reactions to drugs
to a new method of diagnosing drug reactions by the CellScan system.
Methods: The study entailed 21 patients who were diagnosed as
suffering from drug eruptions, and 105 healthy controls with no history of drug
allergy. The drugs were classified into two groups according to suspicion of
causing drug allergy: high and low. Most of the patients were on more than
one drug, leading to 41 patient-drug interactions (assays). Histamine
releasing test (HRT), interferon (INF)-γ releasing test and CellScan
examination were performed on lymphocytes of the patients and controls.
Results: The HRT was interpreted as positive in 9 out of 18 (50%)
patients and in 13 out of 35 (37%) assays. Based on the INF-γ releasing test,
positive results were observed in 16 out of 21 (76%) patients and in 24 out of 41
(59%) assays. In the CellScan test (CST), positive results were observed in 17
out of 21 (81%) patients and in 29 out of 41 (71%) assays. The rate of identifying
the drug for eruption in the high suspicion level drugs was 9 out of 22 (41%)
assays in the HRT, 20 out of 24 (83%) assays in the INF-γ releasing test, and 21
out of 24 (87%) studies with the CellScan method. The rate of determining of
the drug that caused the eruption in the low suspicion level drugs was 4 out of
13 (31%) in the HRT, 4 out of 17 (24%) assays in the INF-γ releasing test, and 8
out of 17 (47%) analyses in the CST. When examined
in the CellScan, 99 out of 105 (94%) controls were interpreted as negative.
Conclusion: This preliminary study indicates that the CellScan seems to
be an easy and promising method for the detection of drugs responsible for
adverse skin reactions. In contrast to the HRT and to the Interferon-γ secretion
test, the CellScan method is characterized by its ability to track and monitor
the reaction of individual cells. By measuring the kinetic parameters of selected
cells before and after adding the suspected drug, we were able to identify
the culprit drug. The CellScan method had the highest sensitivity, and the
interferon-γ secretion test had the highest specificity for detection of the culprit
drug. In contrast, the analysis of 105
normal control sera disclosed a high specificity of 94% for the CellScan method. 相似文献
16.
Yael Graif Ronit Confino-Cohen Arnon Goldberg 《Annals of allergy, asthma & immunology》2006,96(1):24-29
BACKGROUND: The decision regarding an immunotherapy regimen for venom-allergic patients is based on the results of skin testing and serum venom specific IgE measurements. However, their reliability has been questioned, and their reproducibility has not been examined. OBJECTIVE: To evaluate the reproducibility and reliability of the results of skin testing and serum venom specific IgE measurement in venom-allergic patients. METHODS: Patients with a systemic reaction after an insect sting were evaluated twice, 2 to 6 weeks apart, by intradermal skin tests and by determination of serum venom specific IgE to Hymenoptera venoms. RESULTS: Thirty-five patients were evaluated 1 to 168 months (mean, 23 months) after the sting reaction. Reproducibility of skin test results for all venoms at the 2 sessions was found in 23 patients (66%). Reproducibility of venom specific IgE results for all venoms was found in 16 (59%) of 27 patients from whom 2 blood samples were available for evaluation. Concordance between skin test and venom specific IgE results for all venoms was found in 30 (51%) of 59 samples available for evaluation. CONCLUSIONS: The reproducibility of venom skin test and serum venom specific IgE results is relatively poor. It is common practice for therapeutic decisions regarding venom immunotherapy to be based on a single diagnostic evaluation. Consequently, many patients are either overtreated or undertreated. Better diagnostic methods are required in venom allergy. 相似文献
17.
Deborah Elstein Judith Guedalia Glen M Doniger Ely S Simon Vered Antebi Yael Arnon Ari Zimran 《Genetics in medicine》2005,7(2):124-130
PURPOSE: Because of concern for drug-induced cognitive dysfunction during clinical trials using substrate reduction therapy (miglustat) in type 1 Gaucher disease and because it has been suggested that some patients with type 1 Gaucher disease may develop neurocognitive impairment as part of the natural history, two different batteries of neuropsychological tests were devised to examine these issues. Using these tests, cognitive function was assessed in patients treated with miglustat, in patients receiving enzyme replacement (standard care for symptomatic patients), and in untreated (milder) patients. METHODS: For this study, 55/60 patients exposed to miglustat in Israel participated in psychologist-administered testing; 36/55 participated in computerized testing. Of these, 31 enzyme-treated patients and 22 untreated patients participated in the psychologist-administered testing, and 15 enzyme-treated patients and 18 untreated patients participated in computerized testing. The psychologist-administered battery consisted of 18 standard neuropsychological subtests specific to executive and visuospatial functioning. The computerized battery (Mindstreams, NeuroTrax Corp., New York, NY) consisted of 10 subtests tapping multiple cognitive domains. Between-group analyses for each modality compared cognitive performance. RESULTS: In the psychologist-administered testing, patients exposed to miglustat performed significantly less well than the other groups in 5/18 subtests. On the computerized tests, all patients performed comparably to normal controls. Scores in patients exposed to miglustat were higher than in untreated patients, particularly in visuospatial function, whereas enzyme-treated patients performed less well. However, with the exception of visuospatial function, these results were not statistically significant. CONCLUSIONS: It is unclear why different testing methods yielded discordant results. Any dysfunction suggested by the current study is apparently subtle and of doubtful clinical relevance given that cognitive status did not interfere with patients' daily intellectual function. The computerized battery has methodological advantages (e.g., language options, objectivity, brevity, and ease of use) that make it well-suited for longitudinal studies, for long-term surveillance of substrate reduction therapy as well as for comparisons with other lysosomal storage disorders and other chronic diseases. These preliminary findings should allay fears of cognitive dysfunction due to short-term miglustat therapy. 相似文献
18.
The parameters that characterize the intricate water diffusion in tumors may serve to reveal their distinct pathology. Specifically, the application of diffusion magnetic resonance imaging (MRI) can aid in characterizing breast cancer, as well as monitoring response to therapy. We present here a non-invasive, quantitative MRI investigation, at high spatial resolution, of water diffusion in hormonal dependent MCF7 breast tumors implanted orthotopically in immunodeficient mice. Distinctive MRI protocols were designed in this study, utilizing a broad range of diffusion times and diffusion gradient strengths. Application of these protocols allowed water diffusion in the tissue extracellular and intracellular compartments to be distinguished, and the effect of restricted diffusion and water exchange on the water diffusion in these compartments to be evaluated. Pixel-by-pixel analysis yielded parametric maps of the estimated volume fraction and apparent diffusion coefficient of each compartment. The diffusion of the water in the extracellular microenvironment was approximately two fold slower than that of free water, and in the intracellular compartment was about one order of magnitude slower than that of free water and demonstrated restriction of water diffusion at long diffusion times. Mapping of the water fraction in each compartment was further employed to monitor changes during tumor progression and to assess tumor response to hormonal manipulation with a new antiestrogenic drug, tamoxifen methiodide (TMI). It was found that, in parallel to the growth arrest by this drug, the volume fraction of the slowly diffusing water increased, suggesting a TMI-induced cell swelling. This study can serve as a basis for extending diffusion breast MRI in the clinical setting. 相似文献
19.
Mika Shapira Rootman Yael Goldberg Rony Cohen Nesia Kropach Inbal Keidar Rivka Friedland Gad Dotan Osnat Konen Helen Toledano 《Clinical genetics》2020,97(2):296-304
Constitutional mismatch repair deficiency is a rare cancer predisposition syndrome caused by biallelic mutations in one of the four mismatch repair genes. Patients are predisposed to various tumors including hematological malignancies, brain tumors and colorectal carcinomas. Phenotypic overlap with Neurofibromatosis-1 is well known, with most patients presenting with café-au-lait macules. Other common features include axillary and/or inguinal freckling and intracranial MRI foci of high T2W/FLAIR signal intensity similar to the typical FASI seen in Neurofibromatosis-1. In this cohort of eight patients with constitutional mismatch repair deficiency we describe overlapping phenotypical features with Tuberous Sclerosis complex. In addition to “ash-leaf like” hypomelanotic macules (five patients), we detected intracranial tuber-like lesions (three patients), renal cysts (three patients) and renal angiomyolipomas (two patients). All our patients also had Neurofibromatosis-1 like features, mainly café-au-lait macules. This study suggests that features of Tuberous sclerosis especially when overlapping with those of Neurofibromatosis 1 or malignancies atypical for these syndromes should raise the possibility of constitutional mismatch repair deficiency. Correct diagnosis is essential for appropriate genetic counseling and pre-emptive cancer surveillance. 相似文献
20.