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51.
Seven patients with fibromuscular dysplasia of the internal carotid arteries have been operated upon at Walter Reed Army Medical Center. One lesion was treated by graduated dilatation with Bake's dilators combined with resection, end-to-end anastomosis, and vein patching of a tortuous segment. All other lesions were treated by graduated dilatation with an arterial dilator-shunt. All of these patients are asymptomatic presently. One patient has been operated upon recently because of symptoms related to the previously unoperated side as well as mild symptoms related to the previous operation. Two other patients with arteriographic evidence of fibromuscular dysplasia are being followed clinically. One is asymptomatic and one has minimal symptoms. Both are being treated with acetylsalicylic acid in hopes of preventing microembolization from these lesions. Important technical considerations in treating this condition are meticulous dissection of the internal carotid artery as near to the base of the skull as possible, confining the arteriotomy to the region of the carotid bulb, and straightening the carotid artery while passing the dilator under direct vision. A technique for routine shunting in these patients now is available. 相似文献
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Intracranial dural empyema is a neurosurgical emergency with potentially devastating complications. The prognosis is adversely affected by delay in diagnosis. Modern imaging techniques, especially contrast enhanced CT and MRI, have improved the speed and accuracy of radiological diagnosis of this condition, with an associated reduction in mortality. Despite this, there may still be a delay in diagnosis, partly owing to the subtlety of early radiological signs, especially on unenhanced CT. We present cases that illustrate some of the radiological manifestations, complications and potential pitfalls in diagnosis. 相似文献
54.
C. Sukonpan T. Oost M. Goodnough W. Tepp E.A. Johnson D.H. Rich 《Chemical biology & drug design》2004,63(2):181-193
Abstract: Botulinum neurotoxin (BoNT) metalloproteases and related proteases are the most selective proteases known. X‐ray crystal structures suggest that the active sites of the native enzymes exist in catalytically incompetent forms that must be activated by substrate binding. In order to characterize the postulated substrate‐induced conformational changes for enzyme activation, we synthesized a series of transition‐state analog inhibitors in which the dipeptide cleavage site is replaced by tetrahedral intermediate analogs within the minimal substrate peptide sequence. In this paper, we report our efforts to design inhibitors of BoNT/A metalloprotease. We confirm that an effective substrate sequence for BoNT/A metalloprotease is a 17‐mer peptide corresponding to residues 187–203 of SNAP‐25. A more stable substrate, Nle202SNAP‐25 [187–203] was synthesized in order to develop an assay for proteolytic activity of BoNT/A metalloprotease that can be used to monitor time‐dependent inhibition. α‐Thiol amide analogs of Gln‐197 were incorporated via solid‐phase peptide synthesis into both 17‐mer minimal peptide substrate sequences. The synthesis, characterization and inhibition kinetics for the α‐thiol amide analogs of holotoxin A substrate are described. These substrate‐derived inhibitors were shown to be submicromolar inhibitors of BoNT/A catalytic activity. 相似文献
55.
Phase II trial of gefitinib in recurrent glioblastoma. 总被引:13,自引:0,他引:13
Jeremy N Rich David A Reardon Terry Peery Jeannette M Dowell Jennifer A Quinn Kara L Penne Carol J Wikstrand Lauren B Van Duyn Janet E Dancey Roger E McLendon James C Kao Timothy T Stenzel B K Ahmed Rasheed Sandra E Tourt-Uhlig James E Herndon James J Vredenburgh John H Sampson Allan H Friedman Darell D Bigner Henry S Friedman 《Journal of clinical oncology》2004,22(1):133-142
PURPOSE: To evaluate the efficacy and tolerability of gefitinib (ZD1839, Iressa; AstraZeneca, Wilmington, DE), a novel epidermal growth factor receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma. PATIENTS AND METHODS: This was an open-label, single-center phase II trial. Fifty-seven patients with first recurrence of a glioblastoma who were previously treated with surgical resection, radiation, and usually chemotherapy underwent an open biopsy or resection at evaluation for confirmation of tumor recurrence. Each patient initially received 500 mg of gefitinib orally once daily; dose escalation to 750 mg then 1,000 mg, if a patient received enzyme-inducing antiepileptic drugs or dexamethasone, was allowed within each patient. RESULTS: Although no objective tumor responses were seen among the 53 assessable patients, only 21% of patients (11 of 53 patients) had measurable disease at treatment initiation. Seventeen percent of patients (nine of 53 patients) underwent at least six 4-week cycles, and the 6-month event-free survival (EFS) was 13% (seven of 53 patients). The median EFS time was 8.1 weeks, and the median overall survival (OS) time from treatment initiation was 39.4 weeks. Adverse events were generally mild (grade 1 or 2) and consisted mainly of skin reactions and diarrhea. Drug-related toxicities were more frequent at higher doses. Withdrawal caused by drug-related adverse events occurred in 6% of patients (three of 53 patients). Although the presence of diarrhea positively predicted favorable OS from treatment initiation, epidermal growth factor receptor expression did not correlate with either EFS or OS. CONCLUSION: Gefitinib is well tolerated and has activity in patients with recurrent glioblastoma. Further study of this agent at higher doses is warranted. 相似文献
56.
Plasma vitamin B-12 concentrations relate to intake source in the Framingham Offspring study 总被引:1,自引:0,他引:1
Tucker KL Rich S Rosenberg I Jacques P Dallal G Wilson PW Selhub J 《The American journal of clinical nutrition》2000,71(2):514-522
BACKGROUND: Low vitamin B-12 status is prevalent among the elderly, but few studies have examined the association between vitamin B-12 status and intake. OBJECTIVE: We hypothesized that vitamin B-12 concentrations vary according to intake source. DESIGN: Plasma concentrations and dietary intakes were assessed cross-sectionally for 2999 subjects in the Framingham Offspring Study. The prevalence of vitamin B-12 concentrations <148, 185, and 258 pmol/L was examined by age group (26-49, 50-64, and 65-83 y), supplement use, and the following food intake sources: fortified breakfast cereal, dairy products, and meat. RESULTS: Thirty-nine percent of subjects had plasma vitamin B-12 concentrations <258 pmol/L, 17% had concentrations <185 pmol/L, and 9% had concentrations <148 pmol/L, with little difference between age groups. Supplement users were significantly less likely than non-supplement-users to have concentrations <185 pmol/L (8% compared with 20%, respectively). Among non-supplement-users, there were significant differences between those who consumed fortified cereal >4 times/wk (12%) and those who consumed no fortified cereal (23%) and between those in the highest and those in the lowest tertile of dairy intake (13% compared with 24%, respectively), but no significant differences by meat tertile. Regression of plasma vitamin B-12 on log of intake, by source, yielded significant slopes for each contributor adjusted for the others. For the total group, b = 40.6 for vitamin B-12 from vitamin supplements. Among non-supplement-users, b = 56.4 for dairy products, 35.2 for cereal, and 16.7 for meat. Only the meat slope differed significantly from the others. CONCLUSIONS: In contrast with previous reports, plasma vitamin B-12 concentrations were associated with vitamin B-12 intake. Use of supplements, fortified cereal, and milk appears to protect against lower concentrations. Further research is needed to investigate possible differences in bioavailability. 相似文献
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58.
BA Evans IA Hughes CL Bevan MN Patterson JW Gregory 《Archives of disease in childhood》1997,76(6):529-531
The androgen insensitivity syndrome is a heterogeneous disorder with a wide spectrum of phenotypic abnormalities, ranging from complete female to ambiguous forms that more closely resemble males. The primary abnormality is a defective androgen receptor protein due to a mutation of the androgen receptor gene. This prevents normal androgen action and thus leads to impaired virilisation. A point mutation of the androgen receptor gene affecting two siblings with partial androgen insensitivity syndrome is described. One had cliteromegaly and labial fusion and was raised as a girl, whereas the other sibling had micropenis and penoscrotal hypospadias and was raised as a boy. Both were shown to have the arginine 840 to cysteine mutation. The phenotypic variation in this family is thus dependent on factors other than abnormalities of the androgen receptor gene alone. 相似文献
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60.
OBJECTIVE: Because survival from admission to discharge does not provide parents and physicians information about future life expectancy in the premature neonate, we characterized the actuarial survival, defined as the future life expectancy from a given postnatal age, in a large inborn population of premature infants < 30 weeks' gestation. STUDY DESIGN: We determined daily actuarial survival of 1925 inborn infants (23 to 29 weeks' gestation) admitted to the Baylor Affiliated Nurseries from July 1986 through December 1994, stratified by 100-g birth weight and by 1-week gestational-age intervals. RESULTS: In the 501- to 600-g birth weight stratum, actuarial survival improved from 31% at birth, to 61% on day of life 7, and then to 75% on day of life 28; in the 901- to 1000-g birth weight stratum, actuarial survival improved from 88%, to 94%, and then to 98% throughout the same times, respectively. Similar trends were obtained when data were stratified by gestational age. CONCLUSIONS: Survival in the smallest infants improves dramatically during the first few days of life, but there is a significant risk for late death in the smallest of these infants. 相似文献