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11.
The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis 总被引:105,自引:0,他引:105
Steinbach G Lynch PM Phillips RK Wallace MH Hawk E Gordon GB Wakabayashi N Saunders B Shen Y Fujimura T Su LK Levin B Godio L Patterson S Rodriguez-Bigas MA Jester SL King KL Schumacher M Abbruzzese J DuBois RN Hittelman WN Zimmerman S Sherman JW Kelloff G 《The New England journal of medicine》2000,342(26):1946-1952
BACKGROUND: Patients with familial adenomatous polyposis have a nearly 100 percent risk of colorectal cancer. In this disease, the chemopreventive effects of nonsteroidal antiinflammatory drugs may be related to their inhibition of cyclooxygenase-2. METHODS: We studied the effect of celecoxib, a selective cyclooxygenase-2 inhibitor, on colorectal polyps in patients with familial adenomatous polyposis. In a double-blind, placebo-controlled study, we randomly assigned 77 patients to treatment with celecoxib (100 or 400 mg twice daily) or placebo for six months. Patients underwent endoscopy at the beginning and end of the study. We determined the number and size of polyps from photographs and videotapes; the response to treatment was expressed as the mean percent change from base line. RESULTS: At base line, the mean (+/-SD) number of polyps in focal areas where polyps were counted was 15.5+/-13.4 in the 15 patients assigned to placebo, 11.5+/-8.5 in the 32 patients assigned to 100 mg of celecoxib twice a day, and 12.3+/-8.2 in the 30 patients assigned to 400 mg of celecoxib twice a day (P=0.66 for the comparison among groups). After six months, the patients receiving 400 mg of celecoxib twice a day had a 28.0 percent reduction in the mean number of colorectal polyps (P=0.003 for the comparison with placebo) and a 30.7 percent reduction in the polyp burden (the sum of polyp diameters) (P=0.001), as compared with reductions of 4.5 and 4.9 percent, respectively, in the placebo group. The improvement in the extent of colorectal polyposis in the group receiving 400 mg twice a day was confirmed by a panel of endoscopists who reviewed the videotapes. The reductions in the group receiving 100 mg of celecoxib twice a day were 11.9 percent (P=0.33 for the comparison with placebo) and 14.6 percent (P=0.09), respectively. The incidence of adverse events was similar among the groups. CONCLUSIONS: In patients with familial adenomatous polyposis, six months of twice-daily treatment with 400 mg of celecoxib, a cyclooxygenase-2 inhibitor, leads to a significant reduction in the number of colorectal polyps. 相似文献
12.
Catt SL; Sakkas D; Bizzaro D; Bianchi PG; Maxwell WM; Evans G 《Molecular human reproduction》1997,3(9):821-825
Controlling the sex of offspring by the separation of X and Y
chromosome-bearing spermatozoa using flow cytometry has been reported as a
clinical technique aiding prevention of X-linked diseases. Although this
technique has resulted in several hundred normal births in animals and at
least one human birth, there is still concern over its genetic safety due
to the involvement of two potentially mutagenic agents: UV light and the
fluorochrome dye, Hoechst 33342 (H33342). Human spermatozoa, particularly
those considered abnormal, may be more likely to suffer DNA damage
following exposure to mutagenic agents, compared with other mammalian
species. The stability of normal fresh and decondensed human spermatozoa
were examined after exposure to a range of levels of UV and H33342
staining, using an assay that detects endogenous nicks in the DNA of
spermatozoa. The stability of abnormal and normal, fresh and frozen-thawed
human spermatozoa was examined following UV laser, H33342 staining and flow
cytometry treatments utilizing the same assay. There was an increase in the
presence of endogenous nicks when spermatozoa were decondensed compared
with fresh spermatozoa. There was no increase in the incidence of nicks in
any group of spermatozoa after UV and fluorochrome exposure compared with
controls without exposure.
相似文献
13.
Winberg JO; Hammami-Hauasli N; Nilssen O; Anton-Lamprecht I; Naylor SL; Kerbacher K; Zimmermann M; Krajci P; Gedde-Dahl T Jr; Bruckner-Tuderman L 《Human molecular genetics》1997,6(7):1125-1135
Dystrophic epidermolysis bullosa (EBD) is a clinically heterogeneous skin
disorder, characterized by abnormal anchoring fibrils (AF) and loss of
dermal-epidermal adherence. EBD has been linked to the COL7A1 gene at
chromosome 3p21 which encodes collagen VII, the major component of the AF.
Here we investigated two unrelated EBD families with different clinical
phenotypes and novel combinations of recessive and dominant COL7A1
mutations. Both families shared the same recessive heterozygous 14 bp
deletion at the exon-intron 115 boundary of the COL7A1 gene. The deletion
caused in-frame skipping of exon 115 and the elimination of 29 amino acid
residues from the pro-alpha1(VII) polypeptide chain. As a result,
procollagen VII was not converted to collagen VII and the C-terminal NC-2
propeptide which is normally removed from the procollagen VII prior to
formation of the anchoring fibrils was retained in the skin. All affected
individuals also carried missense mutations in exon 73 of COL7A1 which lead
to different glycine- to-arginine substitutions in the triple-helical
domain of collagen VII. Combination of the deletion mutation with a G2009R
substitution resulted in a mild phenotype. In contrast, combination of the
deletion with a G2043R substitution led to a severe phenotype. The G2043R
substitution was a de novo mutation which alone caused a mild phenotype.
Thus, different combinations of dominant and recessive COL7A1 mutations can
modulate disease activity of EBD and alter the clinical presentation of the
patients.
相似文献
14.
Dylan J. Jester Lindsay J. Peterson David M. Dosa Kathryn Hyer 《Journal of the American Medical Directors Association》2021,22(6):1317-1321.e2
ObjectivesTo report the initial compliance with new infection control regulations and geographic disparities in nursing homes (NHs) in the United States.DesignRetrospective cohort study from November 27, 2017 to November 27, 2019.Setting and ParticipantsIn total, 14,894 NHs in the continental United States comprising 26,201 inspections and 176,841 deficiencies.MethodsWe measured the cumulative incidence of receiving F880: Infection Prevention and Control deficiencies, geographic variability of F880 citations across the United States, and the scope and severity of the infection control deficiencies.ResultsA total of 6164 NHs (41%) in the continental United States received 1 deficiency for F880, and 2300 NHs (15%) were cited more than once during the 2-year period. Geographic variation was evident for F880 deficiencies, ranging from 20% of NHs in North Carolina to 79% of NHs in West Virginia. Between 0% (Vermont) and 33% (Michigan) of states’ NHs were cited multiple times over 2 years. Facilities receiving 2 or more F880 deficiencies were more reliant on Medicaid, for-profit, and served more acute residents. Infection Prevention and Control deficiencies were of similar severity but of greater scope in NHs that were cited multiple times.Conclusions and ImplicationsAs the coronavirus disease 2019 pandemic challenges hospitals with an increased surge of patients from the community, NHs will be asked to accept convalescing patients who were previously infected with the virus. NHs will need to rely on infection control practices to mitigate the effects of the virus in their facilities. Particular attention to NHs that have fared poorly with repeat infection control practices deficiencies might be a good first step to improving care overall and preventing downstream morbidity and mortality among the highest-risk patients. 相似文献
15.
Proteoglycan synthesis by bovine keratocytes and corneal fibroblasts: maintenance of the keratocyte phenotype in culture. 总被引:6,自引:0,他引:6
M P Beales J L Funderburgh J V Jester J R Hassell 《Investigative ophthalmology & visual science》1999,40(8):1658-1663
PURPOSE: To determine the effect of serum on morphology, growth, and proteoglycan synthesis by primary cultures of collagenase-isolated bovine keratocytes. METHODS: Keratocytes were isolated from bovine corneas using sequential collagenase digestion and cultured in Dulbecco's modified Eagle's medium (DMEM), with and without fetal bovine serum (FBS). Proteoglycans synthesized by the cells in culture and by keratocytes in intact cornea culture were metabolically radiolabeled with 35SO4. The proteoglycans were characterized by their sensitivity to keratanase, chondroitinase ABC, and heparatinase and by their size on Superose 6 HR. Cell number was determined by measuring DNA content of the culture dishes. RESULTS: Keratocytes cultured in 10% FBS proliferated, appeared fibroblastic, and synthesized only 9% of the total glycosaminoglycan as keratan sulfate (KS), whereas cells in serum-free media were quiescent, appeared dendritic, and synthesized 47% KS, a value similar to the 45% KS for corneas radiolabeled overnight in organ culture. This increased proportion of KS synthesis in serum-free media was caused by a moderate increase in KS synthesis combined with a substantial decrease in chondroitin sulfate (CS) synthesis. Fractionation on Superose 6 High Resolution showed the size and relative amounts of the CS- and KS-containing proteoglycans synthesized by keratocytes in serum-free media also more closely resembled that of keratocytes in corneas in organ culture than keratocytes in media containing serum. CONCLUSIONS: A comparison of proteoglycan synthesis and cell morphology between keratocytes in corneas in organ culture and in cell culture indicates that keratocytes maintain a more native biosynthetic phenotype and appearance when cultured in serum-free media. These results also suggest that culturing in the presence of serum fundamentally alters the keratocyte phenotype to an activated cell, mimicking certain changes observed during wound healing. 相似文献
16.
PURPOSE: Previous studies suggest that proteins associated with the apical junctional complex (AJC) play essential roles in the development, maintenance and regulation of barrier function in transport epithelium and vascular endothelium. The goal of this study is to identify and determine the spatial organization of several major AJC-associated proteins in normal human and feline corneal endothelium. METHODS: Fresh corneal tissue was obtained from 4 recipient buttons removed during penetrating keratoplasty (two from keratoconus patients, and two from patients with post-traumatic stromal scarring) as well as from 16 cat eyes. En bloc double- and triple-labeling of corneas was performed using phalloidin, and mouse, rat or rabbit antibodies to ZO-1, occludin, pan-cadherin, alpha-catenin, beta-catenin and plakoglobin (gamma-catenin). The 3-D localization of the proteins was then determined in situ using laser confocal microscopy. RESULTS: Similar staining patterns were obtained for the corneal endothelium of normal cat corneas and fresh human buttons. Apically, f-actin was arranged into dense peripheral bands (DPB) in individual cells that were separated from those in adjacent cells. Diffuse phalloidin staining also extended from the DPB into the cytoplasm apically. Although weaker, phalloidin staining also appeared to be associated with the basolateral cell borders. The adherens junction protein, cadherin, formed a thin pericellular band at the apical cell junctions between the DPB. In addition, cadherin staining also appeared to extend along the basolateral cell borders in a convoluted pattern. Staining for alpha-catenin, beta-catenin and plakoglobin each showed a nearly identical organization as cadherin. ZO-1 formed a single apical band that was localized between the DPB; however, no basolateral ZO-1 staining was detected. Interestingly, the distribution of ZO-1 was discontinuous around the cell, with the largest gaps occurring at the Y-junctions between adjacent endothelial cells. Positive staining for occludin was not detected in either human or feline corneal endothelium. CONCLUSIONS: The composition and organization of the AJC of corneal endothelium appears to be different from that of classical transport epithelia; these findings may be related to functional differences between these two cell types. 相似文献
17.
18.
Wang WS; Hsieh RK; Chiou TJ; Liu JH; Fan FS; Yen CC; Tung SL; Chen PM 《Japanese journal of clinical oncology》1998,28(9):551-554
A 54-year-old man was treated with weekly 24-h infusion of high-dose
5-fluorouracil (2600 mg/m2) and leucovorin (100 mg/m2) for metastatic colon
cancer. At first, he tolerated the treatment well and no significant
toxicity was identified. After a total of eight courses of treatment, a
stable disease was observed, but mild shortness of breath was found on
occasion. The patient had no previous history of cardiac disease and the
heart performance assessed by left ventricular ejection fraction before
treatment was normal. Unfortunately, acute pulmonary edema with lethal
cardiogenic shock occurred during the ninth course of treatment, in spite
of intensive medical treatment. The chest X-ray showed extreme
cardiomegaly. Repeated assessment of his heart function by echocardiogram
and ventricular ejection fraction revealed a very poor cardiac performance.
Toxic cardiogenic shock during weekly 24-h infusion of high-dose
5-fluorouracil and leucovorin is extremely rare. To the best of our
knowledge, no case has been reported in the English literature. We report a
case and the relevant literature about the incidence, clinical picture and
possible pathophysiology on 5-fluorouracil-related cardioxicity is
reviewed.
相似文献
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