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The computed tomography (CT)/discograms and discographic pain provocation reports of 291 clinical patients, 790 discs (mean age, 38; range, 17-79) were collected. The CT/discograms were classified separating anular disruption and degeneration and recording the pain provoked during discography as no pain, dissimilar, similar, or exact reproduction of the patient's clinical pain. Nondegenerated discs usually were found to be painless, and deteriorated discs painful. The proportion of severely degenerated but painless discs increased with age, as did the discs producing dissimilar pain. This may help explain the poor correlation of low-back pain with radiographic degenerative changes reported in previous epidemiologic studies.  相似文献   
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We previously reported that transplantation (Tx) of prevascularized donor islets as composite islet‐kidneys (IK) reversed diabetic hyperglycemia in both miniature swine and baboons. In order to enhance this strategy's potential clinical applicability, we have now combined this approach with hematopoietic stem cell (HSC) Tx in an attempt to induce tolerance in nonhuman primates. IKs were prepared by isolating islets from 70% partial pancreatectomies and injecting them beneath the autologous renal capsule of five rhesus monkey donors at least 3 months before allogeneic IK Tx. HSC Tx was performed after mobilization and leukapheresis of the donors and conditioning of the recipients with total body irradiation, T cell depletion, and cyclosporine. One IK was harvested for histologic analysis and four were transplanted into diabetic recipients. IK Tx was performed either 20–22 (n = 3) or 208 (n = 1) days after HSC Tx. All animals accepted IKs without rejection. All recipients required >20 U/day insulin before IK Tx to maintain <200 mg/dL, whereas after IK Tx, three animals required minimal doses of insulin (1–3 U/day) and one animal was insulin free. These results constitute a proof‐of‐principle that this IK tolerance strategy may provide a cure for both end‐stage renal disease and diabetes without the need for immunosuppression.  相似文献   
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BACKGROUND: Hepatocyte growth factor (HGF) is a pleiotropic protein with renoprotective functions, which have been attributed at least in part to its ability to counteract the profibrotic effects of transforming growth factor beta (TGF-beta). A major downstream mediator of TGF-beta is connective tissue growth factor (CTGF). However, the molecular mechanisms of CTGF regulation by HGF have not yet been investigated. METHODS: CTGF expression was analysed in human primary tubular epithelial cells (hPTECs) and the cell line HKC-8 by western blotting. Morphological alterations were analysed by immunocytochemistry. RESULTS: HGF induced a transient expression of CTGF, which was maximal after 6 h and returned to baseline after 24 h. Coincubation with TGF-beta increased CTGF protein at 6 h, whereas HGF significantly decreased CTGF induction by TGF-beta after 24 h. Furthermore, HGF induced cell scattering associated with reorganization of focal adhesions and formation of lamellipodia and filopodia. The early induction of CTGF was linked to the HGF-mediated alterations of cell morphology. The PP2 inhibitor of Src-family kinases, which regulate focal adhesion turnover, reduced HGF-mediated upregulation of CTGF. In addition, inhibition of the Rho-kinase, which modulates the actin cytoskeleton, impaired CTGF expression. Combination of both inhibitors further decreased CTGF expression. Comparable inhibitory effects were obtained, when CTGF was induced by the combination of HGF and TGF-beta. CONCLUSIONS: We provide evidence for a dual effect of HGF on CTGF regulation in human tubular epithelial cells: transient upregulation of CTGF in the absence of TGF-beta, which was related to alterations of cell morphology, and interference with TGF-beta-mediated CTGF induction after prolonged incubation.  相似文献   
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Objective: Functional magnetic resonance imaging (fMRI) studies have documented abnormalities in the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex in bipolar disorder in the context of working memory tasks. It is increasingly recognized that DLPFC regions play a role in mood regulation and the integration of emotion and cognition. The purpose of the present study was to investigate with fMRI the interaction between acute sadness and working memory functioning in individuals with bipolar disorder. Methods: Nine depressed individuals with DSM‐IV bipolar I disorder (BP‐I) and 17 healthy control participants matched for age, gender, education, and IQ completed a 2‐back working memory paradigm under no mood induction, neutral state, or acute sadness conditions while undergoing fMRI scanning. Functional MRI data were analyzed with SPM2 using a random‐effects model. Results: Behaviorally, BP‐I subjects performed equally well as control participants on the 2‐back working memory paradigm. Compared to control participants, individuals with BP‐I were characterized by more sadness‐specific activation increases in the left DLPFC (BA 9/46) and left dorsal anterior cingulate (dACC). Conclusions: Our study documents sadness‐specific abnormalities in the left DLPFC and dACC in bipolar disorder that suggest difficulties in the integration of emotion (sadness) and cognition. These preliminary findings require further corroboration with larger sample sizes of medication‐free subjects.  相似文献   
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The distance that separates alphabeta protomers of the Na(+), K(+)-ATPase in microsomes and in purified membranes prepared from duck nasal salt glands was estimated by measuring fluorescence resonance energy transfer between anthroylouabain bound to a population of alphabeta protomers and either N-[7-nitrobenz-2-oxa-1, 3-diazol-4-yl]-6-aminohexyl ouabain or 5-(and-6)-carboxyfluorescein-6-aminohexyl ouabain bound to the rest. Energy transfer between probes bound in the microsomal preparation was less than in the purified membranes. The efficiency of energy transfer between anthroylouabain and N-[7-nitrobenz-2-oxa-1, 3-diazol-4-yl]-6-aminohexyl ouabain was 29.2% in the microsomes compared with 62.6% in the purified preparation. Similar results were obtained with 5-(and-6)-carboxyfluorescein-6-aminohexyl ouabain as acceptor. We calculate that either the protomer bound probes were on the average 13 A farther apart in the microsomes than in the purified membranes, or that 53% of the protomers are monomeric in the microsome preparation. Microsomes prepared in the presence of phalloidin (a toxin that binds to F actin and stabilizes the actin-based cytoskeleton) showed less quench than those prepared in its absence. The data support the hypothesis that protomers are kept apart by their association with the cytoskeleton. The turnover rate while hydrolyzing ATP is the same in the microsomal and purified preparations; higher oligomer formation has no significant effect on the enzyme reaction mechanism.  相似文献   
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A study of Eustachian tube measurements in infants and children is presented. The study included 33 Eustachian tubes from normal temporal bones and 10 Eustachian tubes from temporal bones harbouring acute otitis media. The temporal bones underwent histologic serial sectioning. The lumen of the Eustachian tube's first portion, i.e. the pharyngeal part, was measured with the aid of a grid mounted on a microscope. These measurements show: A. The Eustachian tube lumen grows and enlarges to a small extent with age. B. Each age group presents a considerable variation in the range of area of the lumen comparable with the natural biological distribution. C. No statistical difference was found between the size of the pharyngeal portion of the lumen of the Eustachian tube from temporal bones which had acute otitis media and those coming from non-pathological ears. This comparison took into consideration age and physiological distribution. These findings are similar to our earlier findings regarding the isthmic region.  相似文献   
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