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81.
BACKGROUND: This investigation examined the possibility that the inhibitory effect of halothane on nonshivering thermogenesis (heat production) in brown adipocytes is not a universal effect of all anesthetic agents but related to the type of anesthetic. METHODS: Brown adipocytes from hamster were isolated with a collagenase digestion method and incubated with anesthetic agents. The rate of oxygen consumption was measured with an oxygen electrode. The effect of clinically relevant (and higher) doses of anesthetics of different classes on basal and norepinephrine-induced thermogenesis (oxygen consumption) was tested. RESULTS: Two distinct groups of anesthetics could be distinguished: thermogenesis inhibitors and noninhibitors. Thermogenesis inhibitors include volatile anesthetics such as halothane (IC(50), 1.1 mm), ether (IC(50), 20 mm), and chloroform (IC(50), 2.2 mm) (nominal concentrations), but also tribromoethanol (IC(50), 0.6 mm), all inducing inhibition of norepinephrine-induced thermogenesis without affecting the EC for norepinephrine. Thermogenesis noninhibitors include the nonvolatile anesthetics pentobarbital, propofol, ketamine, and urethane, the inhalation anesthetic nitrous oxide, and, notably, also the volatile nonanesthetics (nonimmobilizers) 1,2-dichlorohexafluorocyclobutane and 2,3-dichlorooctafluorobutane; none of these compounds had any effect on norepinephrine-induced thermogenesis at any concentration tested. CONCLUSIONS: There are two distinct classes of anesthetics with regard to effects on thermogenesis, thermogenesis inhibitors and thermogenesis noninhibitors. The results are important for the interpretation of studies in thermal biology in general; specifically, they indicate that conclusions concerning regulation of nonshivering thermogenesis during anesthesia depend on the type of anesthetic used. Of clinical importance is that the volatile anesthetics are inhibitory for nonshivering thermogenesis and thus for an alternative heat production when myorelaxants prevent shivering. As the distinction between thermogenesis inhibitors and thermogenesis noninhibitors corresponds to the distinction between volatile and nonvolatile anesthetics, it may be related to the mode of action of the volatile anesthetics. 相似文献
82.
Purpose: The aim of this study was to find out how long it is necessary to follow-up esophageal atresia patients endoscopically to prevent irreversible mucosal changes. Methods: Seventy-four of 79 long-term survivors with esophageal atresia and primary anastomosis underwent a total of 322 esophagogastroduodenoscopies during a follow-up period of 0.5 to 19 years (mean, 10.3) after the primary operation. For analysis, the biopsy findings were divided into 2 groups: good, histologically normal or only mildly inflamed mucosa; unfavorable, moderate or severe esophagitis or gastric metaplasia. Fundoplication irrespective of indications was considered unfavorable. The results were analyzed using actuarial survival analysis; the changing point was when a [ldquo ]good[rdquo ] turned into [ldquo ]unfavorable.[rdquo ] Results: Forty-five patients (61%) remained in the [ldquo ]good[rdquo ] group throughout the study period; 15 of those (20%) had completely normal findings. Nine patients (12%) had moderate, one (1%) had severe esophagitis, and 13 patients (18%) had gastric metaplasia. Fundoplication was performed on 21 patients (28%). Conclusions: About 40% of esophageal atresia patients eventually have significant esophageal mucosal pathology or need to have a fundoplication. The majority of these changes appear before the age of 3 years. Routine endoscopic follow-up of esophageal atresia patients is recommended at least to the age of 3 years. J Pediatr Surg 38:702-704. [copy ] 2003 Elsevier Inc. All rights reserved. 相似文献
83.
84.
Rånby M Ramström S Svensson PO Lindahl TL 《Scandinavian journal of clinical and laboratory investigation》2003,63(6):397-406
An automated procedure for determination of clotting time in whole blood was validated by direct comparison with the reference method, visual clotting time determination. The procedure was based on a 10 Hz free oscillation rheometer (FOR) of our design, the ReoRox 4. Recalcified citrated blood samples (n = 30), clotting in the range 4 to 20 min, were used in the validation. Every 30 s of the analysis, as the change in stiffness (deltaG*) of the sample was monitored by FOR, the sample cup was shortly removed from the FOR and its contents inspected for first signs of clotting, i.e. visual clotting time determination. Various FOR clotting criteria were attempted. Best correlation to visual clotting time was found when deltaG* reached 0.01 Pa, which yielded linear regression slope, intercept and r2 of 0.98, 0.09 min and 0.98, respectively. For comparison, six plasma samples were analyzed in the same way and gave almost the same results. The accuracy of the FOR determinations was checked by also analyzing, in parallel, portions of the sample with a conventional oscillation rheometer, a Bohlin VOR. The rationale is given for preferring deltaG* over G* as a FOR monitoring function in coagulation tests and for including median filtration of the primary FOR data. An extension of the FOR theory to include deltaG* and evidence in support of inhomogeneous blood clotting are also given. 相似文献
85.
The expression of vascular endothelial growth factor correlates with mutant p53 and poor prognosis in human breast cancer 总被引:25,自引:0,他引:25
Linderholm BK Lindahl T Holmberg L Klaar S Lennerstrand J Henriksson R Bergh J 《Cancer research》2001,61(5):2256-2260
Wild-type p53 protein has been shown to inhibit angiogenesis through thrombospondin in the preclinical setting. Here, we determined the associations between the expression of the angiogenic factor vascular endothelial growth factor (VEGF) and the p53 status, including different mutation sites and types, in primary breast cancer. Cytosols from 224 primary breast cancer patients were analyzed with an enzyme immunoassay for determination of human VEGF165 protein content. p53 status was determined by cDNA-based sequencing of the entire coding region, by immunohistochemistry (IHC), and by a p53 luminometric immunoassay (LIA) method. Statistically significant associations was found between higher VEGF content and non-wild-type p53 status for all methods; sequence-based data (P = 0.0019), IHC data (P = 0.0068), and the LIA method (r = 0.427; P > 0.001). Highest VEGF values were detected in tumors with p53 insertions, deletions, and stop codon mutations (P = 0.0043). Combining p53 status and VEGF content resulted in additional prognostic information, relapse-free survival (RFS; P = 0.0377), overall survival (OS; P = 0.0319), and breast cancer corrected survival (BCCS; P = 0.0292). In multivariate analysis, the relative hazard increased when the VEGF data were added to the p53 status, with a relative hazard of 1.7 for RFS and 3.0 for BCCS, compared with 1.1 for RFS and 1.4 for BCCS among the patients with either high VEGF content or p53 mutation. Higher VEGF content was statistically significantly correlated with a worse outcome for patients with estrogen receptor-positive tumors receiving adjuvant tamoxifen: RFS (P = 0.0471), OS (P = 0.0134), BCCS (P = 0.0064), as well as in multivariate analysis with point estimates of 3.4 and 2.1 for BCCS and RFS, respectively. VEGF expression is related to p53 status in human breast cancer patients. Combining VEGF with p53 status resulted in better prognostic prediction. 相似文献
86.
Escherichia coli alkB mutants are very sensitive to DNA methylating agents. Despite these mutants being the subject of many studies, no DNA repair or other function has been assigned to the AlkB protein or to its human homolog. Here, we report that reactivation of methylmethanesulfonate (MMS)-treated single-stranded DNA phages, M13, f1, and G4, was decreased dramatically in alkB mutants. No such decrease occurred when using methylated lambda phage or M13 duplex DNA. These data show that alkB mutants have a marked defect in processing methylation damage in single-stranded DNA. Recombinant AlkB protein bound more efficiently to single- than double-stranded DNA. The single-strand damage processed by AlkB was primarily cytotoxic and not mutagenic and was induced by SN2 methylating agents, MMS, DMS, and MeI but not by SN1 agent N-methyl-N-nitrosourea or by gamma irradiation. Strains lacking other DNA repair activities, alkA tag, xth nfo, uvrA, mutS, and umuC, were not defective in reactivation of methylated M13 phage and did not enhance the defect of an alkB mutant. A recA mutation caused a small but additive defect. Thus, AlkB functions in a novel pathway independent of these activities. We propose that AlkB acts on alkylated single-stranded DNA in replication forks or at transcribed regions. Consistent with this theory, stationary phase alkB cells were less MMS sensitive than rapidly growing cells. 相似文献
87.
L S Lindahl L Bird M E Legare G Mikeska G R Bratton E Tiffany-Castiglioni 《Toxicological sciences》1999,50(2):236-243
The apparent ability of astroglia to serve as a lead (Pb) sink in the mature brain may result from either their strategic location, between the blood-brain barrier and neurons, or from intrinsic differences between the ability of astroglia and neurons to accumulate this metal. This phenomenon may be dependent on the degree of cell differentiation. In order to address the latter possibility, Pb accumulation was compared among the following cell culture models: (1) mature and immature rat astroglia, (2) undifferentiated SY5Y human neuroblastoma cells and SY5Y cells differentiated with nerve growth factor, (3) immature rat astroglia grown in differently conditioned media, some of which induce partial differentiation, and (4) rat astroglia and SY5Y cells in co-culture. Astroglial cultures, prepared from 1-day-old rat cerebral hemispheres, were exposed to 1 microM Pb after either 14 (immature) or 21 (mature) days in culture. Pb content of the cells was measured by atomic absorption spectroscopy. Immature astroglia took up less Pb when glutathione (GSH) was added to the medium, suggesting that GSH may regulate Pb uptake in these cells. Undifferentiated neuroblastoma cells accumulated more Pb than did the differentiated ones. Astroglia accumulated up to 24 times more Pb than did neuronal cells. This ability was enhanced by exposure to conditioned medium from a neuroblastoma cell line, but not by endothelial cell-conditioned medium, although this medium induced the expression of a glutamate-activated Ca2+ response. Our findings are in agreement with in vivo studies, and thus validate the use of these cell-culture models for future studies on differential mechanisms of Pb uptake. 相似文献
88.
89.
Zhang X Wang B O'Callaghan P Hjertström E Jia J Gong F Zcharia E Nilsson LN Lannfelt L Vlodavsky I Lindahl U Li JP 《Acta neuropathologica》2012,124(4):465-478
Neuroinflammation is typically observed in neurodegenerative diseases such as Alzheimer's disease, as well as after traumatic injury and pathogen infection. Resident immune cells, microglia and astrocytes, are activated and joined by blood-borne monocytes that traverse the blood-brain barrier and convert into activated macrophages. The activated cells express various cytokines, chemokines and proteolytic enzymes. To study the role of heparan sulfate proteoglycans in neuroinflammation, we employed a transgenic mouse overexpressing heparanase, an endoglucuronidase that specifically degrades heparan sulfate side chains. Neuroinflammation was induced by systemic challenge with lipopolysaccharide, or by localized cerebral microinjection of aggregated amyloid-β peptide, implicated in Alzheimer's disease. Lipopolysaccharide-treated control mice showed massive activation of resident microglia as well as recruitment of monocyte-derived macrophages into the brain parenchyma. Microinjection of aggregated amyloid-β elicited a similar inflammatory response, albeit restricted to the injection site, which led to dispersion and clearance of the amyloid. In the heparanase-overexpressing mice, all aspects of immune cell recruitment and activation were significantly attenuated in both inflammation models, as was amyloid dispersion. Accordingly, an in vitro blood-brain barrier model constructed from heparanase-overexpressing cerebral vascular cells showed impaired transmigration of monocytes compared to a corresponding assembly of control cells. Our data indicate that intact heparan sulfate chains are required at multiple sites to mediate neuroinflammatory responses, and further point to heparanase as a modulator of this process, with potential implications for Alzheimer's disease. 相似文献
90.
0 引言 1989- 0 7全球首例活体肝部分移植术成功以来 ,这一手术先后在 30余个国家和地区开展 ,至 1996 - 0 8全球累计总例数已愈 70 0例 ,我院于 1997- 0 6 - 30在日本京都大学Tanaka Koichi教授的指导下 ,成功地开展了 1例活体肝部分移植术 ,至今患者已健康生存 1.5 a,现就其术后中长期管理结合文献总结如下 :1 临床资料1.1 病例 患者为 10岁女性 ,诊断为先天性弥漫性肝内胆管囊性扩张症、复发性胆管炎、肝硬变症 ,1997- 0 6 - 30在全麻下行活体肝部分移植术 ,供体为患儿 40多岁的父亲 ,手术顺利 ,术后早期临床资料已作过报告 [1 ] … 相似文献