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51.
52.
Khundmiri SJ Weinman EJ Steplock D Cole J Ahmad A Baumann PD Barati M Rane MJ Lederer E 《Journal of the American Society of Nephrology : JASN》2005,16(9):2598-2607
It was demonstrated that expression of murine sodium hydrogen exchanger regulatory factor (NHERF-1) lacking the ezrin-binding domain blocks parathyroid hormone (PTH) regulation of Na+,K+-ATPase in opossum kidney (OK) cells. The hypothesis that the NHERF-1 PDZ domains contribute to PTH regulation of Na+,K+-ATPase was tested by comparison of PTH regulation of Na+,K+-ATPase in wild-type OK (OK-WT) cells, NHERF-deficient OKH cells, OK-WT transfected with siRNA for NHERF (NHERF siRNA OK-WT), and OKH cells that were stably transfected with full-length NHERF-1 or constructs with mutated PDZ domains. OKH cells and NHERF siRNA OK-WT showed decreased expression of NHERF-1 but equivalent expression of ezrin and Na+,K+-ATPase alpha1 subunit when compared with OK-WT cells. PTH decreased Na+,K+-ATPase activity and stimulated phosphorylation of the Na+,K+-ATPase alpha1 in OK-WT cells but not in NHERF-deficient cells. Rubidium (86Rb) uptake was equivalent in OK-WT, OKH, and OKH cells that were transfected with all but the double PDZ domain mutants. PTH decreased 86Rb uptake significantly in OK-WT but not in OKH cells. PTH also significantly inhibited 86Rb uptake in OKH cells that were transfected with full-length NHERF-1 or NHERF-1 with mutated PDZ 2 but not in OKH cells that were transfected with mutated PDZ 1. Transfection with NHERF expressing both mutated PDZ domains resulted in diminished basal 86Rb uptake that was not inhibited further by PTH. PTH stimulated protein kinase Calpha activity and alpha1 subunit phosphorylation in OK-WT but not in NHERF-deficient cells. Transfection of OKH cells with NHERF constructs that contained an intact PDZ1 domain restored PTH-stimulated protein kinase Calpha activity and alpha1 subunit phosphorylation. These results demonstrate that NHERF-1 is necessary for PTH-mediated inhibition of Na+,K+-ATPase activity and that the inhibition is mediated through the PDZ1, not PDZ2, domain. 相似文献
53.
Carotid artery pseudoaneurysm is a rare complication of injury to the head and neck, which has been traditionally managed by an open surgical repair to avoid the occurrence of devastating cerebral strokes. Their treatment presents a challenge because of the risk of serious neurological events. This report presents a case of a stab penetrating injury to the left upper neck (Monson`s zone-III), which resulted in ipsilateral seventh and twelfth cranial nerve palsy and contra lateral hemiparesis, and false aneurysm of the internal carotid artery. After excision of the aneurysm, the internal carotid artery was ligated. The postoperative course was uneventful, and the patient remains free of symptoms. 相似文献
54.
55.
Deane NG Lee H Hamaamen J Ruley A Washington MK LaFleur B Thorgeirsson SS Price R Beauchamp RD 《Cancer research》2004,64(4):1315-1322
Transgenic mice that overexpress cyclin D1 protein in the liver develop liver carcinomas with high penetrance. Transforming growth factor beta (TGF-beta) serves as either an epithelial cell growth inhibitor or a tumor promoter, depending on the cellular context. We interbred LFABP-cyclin D1 and Alb-TGF-beta1 transgenic mice to produce cyclin D1/TGF-beta1 double transgenic mice and followed the development of liver tumors over time, characterizing cellular and molecular changes, tumor incidence, tumor burden, and tumor physiology noninvasively by magnetic resonance imaging. Compared with age-matched LFABP-cyclin D1 single transgenic littermates, cyclin D1/TGF-beta1 mice exhibited a significant increase in tumor incidence. Tumor multiplicity, tumor burden, and tumor heterogeneity were higher in cyclin D1/TGF-beta1 mice compared with single transgenic littermates. Characteristics of cyclin D1/TGF-beta1 livers correlated with a marked induction of the peripheral periductal oval cell/stem cell compartment of the liver. A number of cancerous lesions from cyclin D1/TGF-beta1 mice exhibited unique features such as ductal plate malformations and hemorrhagic nodules. Some lesions were contiguous with the severely diseased background liver and, in some cases, replaced the normal architecture of the entire organ. Cyclin D1/TGF-beta1 lesions, in particular, were associated with malignant features such as areas of vascular invasion by hepatocytes and heterogeneous hyperintensity of signal on T2-weighted magnetic resonance imaging. These findings demonstrate that TGF-beta1 promotes stem cell activation and tumor progression in the context of cyclin D1 overexpression in the liver. 相似文献
56.
RASSF1A interacts with microtubule-associated proteins and modulates microtubule dynamics 总被引:11,自引:0,他引:11
Dallol A Agathanggelou A Fenton SL Ahmed-Choudhury J Hesson L Vos MD Clark GJ Downward J Maher ER Latif F 《Cancer research》2004,64(12):4112-4116
The candidate tumor suppressor gene RASSF1A is inactivated in many types of adult and childhood cancers. However, the mechanisms by which RASSF1A exerts its tumor suppressive functions have yet to be elucidated. To this end, we performed a yeast two-hybrid screen to identify novel RASSF1A-interacting proteins in a human brain cDNA library. Seventy percent of interacting clones had homology to microtubule-associated proteins, including MAP1B and VCY2IP1/C19ORF5. RASSF1A association with MAP1B and VCY2IP1/C19ORF5 was subsequently confirmed in mammalian cell lines. This suggested that RASSF1A may exert its tumor-suppressive functions through interaction with the microtubules. We demonstrate that RASSF1A associates with the microtubules, causing them to exist as hyperstabilized circular bundles. We found that two naturally occurring tumor-associated missense substitutions in the RASSF1A coding region, C65R and R257Q, perturb the association of RASSF1A with the microtubules. The C65R and R257Q in addition to VCY2IP1/C19ORF5 showed reduced ability to induce microtubule acetylation and were unable to protect the microtubules against the depolymerizing action of nocodazole. In addition, wild-type RASSF1A but not the C65R or the R257Q is able to block DNA synthesis. Our data identify a role for RASSF1A in the regulation of microtubules and cell cycle dynamics that could be part of the mechanism(s) by which RASSF1A exerts its growth inhibition on cancer cells. 相似文献
57.
Several subtypes of voltage-dependent calcium channels (VDCCs) are present in the presynaptic terminals. In the mammalian hippocampus, P/Q-, N-, and R- but not L-type VDCCs are involved in the fast transmitter release from large mossy fiber (MF) boutons, which are associated with CA3 pyramidal cell dendrites. We investigated whether L-type VDCCs are indeed absent in these large MF boutons. With the use of Sr2+ as the Ca2+ substitute, the stimulus-evoked Sr2+ increment (delta[Sr2+]pre) was evaluated fluorometrically. Delta[Sr2+]pre appeared to be proportional to Sr2+ inflow through VDCCs and was specifically attenuated by conventional VDCC subtype-selective antagonists. The P/Q-type selective omega-agatoxin IVA (AgTx(IVA)) blocked delta[Sr2+]pre with an IC50 of 28 nM and by 30-35% at its maximum effective concentration of 0.5 microM. The N-type selective omega-conotoxin GVIA (CgTx(GVIA)) blocked delta[Sr2+]pre with an IC50 of 15 nM and by 20-25% at its maximum effective concentration of 1 microM. The R-type selective SNX-482 blocked delta[Sr2+]pre with an IC50 of 79 nM and by 20-25% at its maximum effective concentration of 1 microM. The effects of these toxins did not overlap at their maximum effective concentrations and about 70-80% of delta[Sr +]pre was blocked by the simultaneous exposure to these toxins. delta[Sr2+]pre component that is resistant to AgTx(IVA), CgTx(IVA), and SNX-482 was significantly potentiated by an L-type agonist, (S)-(-)-Bay K8644, and attenuated by an L-type antagonist, nimodipine, suggesting that L-type VDCCs are present in large MF terminals. The L-type agonist, (+/-)-Bay K8644, also potentiated Sr2+ inflow into individual boutons identified as large MF boutons under confocal microscopy. Almost similar results were observed for Ca2+ inflow-dependent fluorescence increments. L-type VDCCs appear to be present in large MF boutons and mediate a substantial Ca2+ inflow into presynaptic terminals during action potentials. 相似文献
58.
Role of efflux pumps and mutations in genes for topoisomerases II and IV in fluoroquinolone-resistant Pseudomonas aeruginosa strains 总被引:1,自引:0,他引:1
We have investigated the occurrence of mutations in topoisomerase II (DNA gyrase) subunit B(gyrB) and topoisomerase IV subunit E(parE) and the hyperexpression of genes for four efflux pump proteins in 20 previously described, fluoroquinolone-resistant clinical strains of Pseudomonas aeruginosa. Amino acid alterations were found in GyrB in five strains and in ParE in three strains with MIC of norfloxacin > or = 8 mg/L, and it is likely that some of the alterations contribute to the quinolone resistance exhibited by these strains. Seventeen of the 20 strains overproduced mRNA for one or more pump proteins (MexB, MexD, MexF, or MexY), which caused multidrug resistance phenotype in more than half of strains. Two strains were hypermutable and one of them was highly resistant, but the other strain was only moderately resistant. 相似文献
59.
Faruqi SA Noumoff MJ Deger RB Jalal SM Antoniades K 《Cancer Genetics and Cytogenetics》2002,132(2):165-168
Mature ovarian teratomas are benign ovarian germ cell tumors that usually present with a normal karyotype. There are very few reports describing chromosomal abnormalities in these tumors, none of which are recurrent. In this study we report on a mature teratoma case with clonal chromosomal alterations which include monosomies of chromosomes 6, 14, 16, and 21; trisomies of chromosomes 14 and 21; and deletions of Xq, 5p, 16p, and 17p. Comparative genomic hybridization evaluation of the sample revealed a normal profile. These findings are discussed together with the cytogenetic reports on other cases of ovarian teratomas described in the literature. 相似文献
60.
Assouad J Barthes Fle P Shaker W Souilamas R Riquet M 《The Annals of thoracic surgery》2003,75(3):986-989
BACKGROUND: Pleural effusion (PE) is a rare complication of advanced liver cirrhosis, which may lead to an operation when uncontrolled. The purpose of this study was to evaluate the modality of the occurrence of pleural effusion and to describe its surgical management. METHODS: We studied 21 patients who were referred to the department of thoracic surgery because of massive and recurrent PE caused by liver cirrhosis. The PE was a transudate in 16 patients and an exudate in 5. Talc pleurodesis was attempted in all patients. The patients were divided into two groups. Video assisted thoracoscopy was performed in 13 patients in whom the clinical condition permitted general anesthesia; the pleural cavity was entirely explored before pleurodesis (group 1). Chest tube drainage alone was performed in 8 patients who were unable to undergo general anesthesia; talc pleurodesis was performed through the chest tube in these patients (group 2). RESULTS: In group 1 the PE was right-sided in 8 patients, left-sided in 3, and bilateral in 2. Diaphragmatic defects were observed in 2 patients, and a fluid leak oozing from the diaphragm was observed in 1 patient. Ten patients were considered cured and were without recurrence. Two patients underwent late recurrence before dying from their liver cirrhosis. Only 1 patient had an early recurrence that was cured by complementary talc slurry. In group 2 all patients presented with a right PE; of these, 3 patients died from septic shock caused by pleural infection. Three patients underwent early recurrence but were cured after repeat talc slurry. One patient had a midterm recurrence. One patient had an early recurrence treated by intrahepatic porto-systemic shunt with partial improvement. CONCLUSIONS: Passage of ascites through diaphragmatic defects appears to be the main cause of PE complicating cirrhosis. Patients may benefit from talc pleurodesis. Video assisted thoracoscopy pleurodesis is the technique of choice with consistent results. Repeated talc injection through the drain may prove useful for patients in poor clinical status. 相似文献