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71.
Neutrophil elastase produces 52-kD and 30-kD glucocorticoid receptor fragments in the cytosol of human leukemia cells 总被引:1,自引:0,他引:1
Characterization of glucocorticoid receptors in leukemia cells is important to understand mechanisms of glucocorticoid resistance but has been impeded by receptor fragmentation in cytosol extracts. We recently found that formation of 52- and 30-kilodalton (kD) glucocorticoid receptor fragments in cytosol of leukemia cells is due to proteolysis and is blocked by diisopropylfluorophosphate (DFP). In the present study, we identify a 28-kD serine protease in cytosol of leukemia cells that binds [3H]DFP and correlates with the formation of 52- and 30-kD receptor fragments. This protease is immunoprecipitated by antiserum to neutrophil elastase. Limited digestion of [3H]dexamethasone-21-mesylate- labeled receptors by purified neutrophil elastase produces 52- and 30- kD receptor fragments. Receptor fragmentation in the cytosol of leukemia cells in inhibited by methoxysuccinyl-alanyl-alanyl-prolyl- valyl-chloromethylketone, a highly specific inhibitor of neutrophil elastase. The addition of as few as 5% neutrophils to a lymphoid cell suspension provides sufficient elastase to produce receptor fragmentation. Our findings indicate that neutrophil elastase is responsible for receptor fragmentation in the cytosol of leukemia cells. The neutrophil elastase may be endogenous to the leukemia cells or may come from neutrophils that contaminate leukemia cell suspensions. 相似文献
72.
Plasmic degradation of crosslinked fibrin has been studied to identify the proteolytic cleavages that convert the clot into a soluble lysate and also to identify the derivatives that are likely to circulate during clot dissolution. Initial polypeptide chain cleavages do not disrupt the solid clot matrix. With continued exposure to plasmin, high molecular weight derivatives are produced that remain attached to the clot by noncovalent forces. Further degradation then results in the liberation into solution of several large, noncovalently bound complexes. Progressive degradation of the largest, initially liberated complexes to the terminal derivatives, DD/E, DD, and E, occurs in solution after their release from the clot. As the fibrin clot is exposed to plasmin for longer intervals, progressive dissolution occurs, but the structure of the covalently bound insoluble fibrin core, the noncovalently attached derivatives, and the liberated complexes remains constant. Since much of the initially liberated protein is in complexes larger than DD/E, these derivatives probably represent the more prevalent plasmic degradation products of crosslinked fibrin in vivo. 相似文献
73.
Chemoattractant-induced changes in surface expression and redistribution of a functional ligand for P-selectin on neutrophils 总被引:4,自引:0,他引:4
Adhesion between platelets and neutrophils is mediated through the interaction of P-selectin on activated platelets with a carbohydrate- containing structure on neutrophils, and occurs under both static and shear conditions. Recent studies using flow chambers have shown that neutrophils become activated after binding to surface-adherent platelets expressing P-selectin. The objective of the present study was to investigate the effect of such activation on the interactions of platelet P-selectin with its ligand on neutrophils. Flow cytometric analyses using P-selectin chimeras revealed that activation induced a rapid and marked reduction in chimera binding, with levels of binding decreased by 71% after 15 minutes of stimulation with the chemotactic agent, FMLP. Using a visual assay of platelet-neutrophil rosetting, we showed that the P-selectin ligand was translocated and clustered at the uropod of neutrophils following the shape changes and polarization induced by chemotactic stimulation. Activated neutrophils bound to surface-adherent platelets also displayed the clustering of P-selectin ligand at the uropod, and these neutrophils detached from the platelets when a shear stress (2 dynes/cm2) was applied through the adhesion chamber. These results indicate that chemotactic stimulation of neutrophils induces changes in the surface expression and distribution of a biologically relevant ligand for P-selectin, and that these changes might influence the adhesive interactions occurring between neutrophils and activated platelets. 相似文献
74.
Nodular mixed lymphoma: results of a randomized trial failing to confirm prolonged disease-free survival with COPP chemotherapy 总被引:2,自引:0,他引:2
Fifty-two patients with stage III or IV nodular mixed lymphocytic- histiocytic lymphoma (NM) were entered on a prospective randomized trial comparing cyclophosphamide-prednisone (CP) to either COPP (cyclophosphamide, vincristine, procarbazine, prednisone) or BCVP (BCNU, cyclophosphamide, vincristine, prednisone). The COPP regimen utilized in this Eastern Cooperative Oncology Group (ECOG) trial was similar to the four-drug regimen C-MOPP reported by the National Cancer Institute to achieve prolonged relapse-free survival in this histology. No significant differences in complete response rates, response duration, or overall survival were noted among the three regimens. A pattern of continuous late relapse was observed for all three chemotherapy programs. Although 11 of the 18 (61%) COPP patients achieved a complete response, only 3/11 (27%) remain disease-free with a median follow-up of over 3 yr. However, two of these three long-term complete responders have died with no clinical evidence of recurrent disease. The COPP patients received 84% of the calculated ideal doses of cyclophosphamide and 78% of the ideal dosage of procarbazine. Grade 3-4 hematologic toxicity was noted in 22% of the COPP group, 36% with BCVP, and 0% for the CP patients. We were unable to confirm the ability of COPP to achieve durable complete remissions in NM lymphoma. The cyclophosphamide-prednisone combination was equally effective when compared with COPP and BCVP, but produced minimal toxicity. 相似文献
75.
Deletions of the cyclin-dependent kinase inhibitor genes p16INK4A and p15INK4B in non-Hodgkin's lymphomas 总被引:7,自引:0,他引:7
The tumor suppressor genes p16INK4A and p15INK4B map to the 9p21 chromosomal locus and are either homozygously deleted or mutated in a wide range of human cancer cell lines and tumors. Although chromosome 9 abnormalities have been described in non-Hodgkin's lymphomas (NHLs), to date, the mutational status of these genes has not been determined for these malignancies. A total of five cell lines and 75 NHLs were examined for homozygous deletions or point mutations in the coding regions of both the p15 and p16 genes using Southern blot and/or polymerase chain reaction-single-strand conformation polymorphism analyses. Homozygous deletions of either the p16 gene or both the p15 and p16 genes were observed in one diffuse large B-cell lymphoma cell line and two uncultured lymphomas consisting of one large B-cell and one mixed T-cell lymphoma. In contrast, point mutations were not detected in either the cell lines or lymphomas. These results indicate that the rate of alterations in the p15 and p16 genes is low for lymphomas, but loss of p16 and/or p15 may be involved in the development of some lymphomas. 相似文献
76.
N-ras gene point mutations in childhood acute lymphocytic leukemia correlate with a poor prognosis 总被引:2,自引:2,他引:2
Lubbert M; Mirro J Jr; Miller CW; Kahan J; Isaac G; Kitchingman G; Mertelsmann R; Herrmann F; McCormick F; Koeffler HP 《Blood》1990,75(5):1163-1169
Ras genes can be altered by point mutations at critical portions of their coding regions to acquire transforming ability in vitro. These point mutations have been detected in a variety of human malignancies. However, their relevance for the clinical and biologic behavior of the subgroups of patients exhibiting these mutations in unclear. We analyzed 100 patients with childhood acute lymphocytic leukemias (ALLs) for point mutations of exons 1 and 2 of all three ras genes (H-ras, K- ras, and N-ras) by polymerase chain reaction and a combination of oligonucleotide hybridization and direct DNA sequencing. A 6% incidence of N-ras gene mutations was detected, all of which occurred at different nucleotides of codons 12 or 13 of N-ras. When correlating presence of ras mutations with the clinical and biologic features and the clinical outcome of these cases, a significantly higher risk for hematologic relapse (P = .01) and a trend toward a lower rate of complete remission (P = .07) was noted. The two groups did not differ in any of the known high-risk factors of ALL. These results suggest that presence of an N-ras mutation in children with ALL may be an independent predictor for worse clinical outcome and therefore may have therapeutic implications; further studies to confirm these findings are required because of the small number of patients with N-ras mutations. 相似文献
77.
Heterotypic adherence between marrow stromal cells (MSC) and lymphoblastic cells is essential for normal lymphopoiesis and malignant lymphoblastic development. However, the detailed molecular mechanisms by which this heterotypic adherence occurs are poorly understood. The cell-cell interactions between a B-lymphoblastic cell line (UTMB-460) and a pre-B-cell line (NALM-6) with MSC were chosen as models to investigate potential mechanisms and adhesion molecules involved in the apposition between normal and malignant lymphoblastic cells and MSC. A parallel-flow detachment assay (PFDA) and a 51Cr detachment assay, coupled with monoclonal antibody (MoAb) blocking experiments, were used to quantify the attachment of lymphoblastic cells to confluent monolayers of MSC. The apposition between MSC and B-lymphoblastic cells (UTMB-460 cells) was investigated for variable time periods, ranging from 1 minute to 4 hours. Results from the temporal study suggest that the heterotypic adherence of the B-lymphoblastic cells to MSC is a biphasic event and the interactions occur rapidly (< or = 1 minute) after the two cells come into contact. More specifically, the early phase of adherence (< or = 15 minutes) solely involves very late antigen-4 alpha (VLA-4 alpha)/vascular cell adhesion molecule 1 (VCAM- 1) interactions, as evidenced by the nearly complete inhibition (93%) of UTMB-460 cell adherence in the presence of anti-VLA-4 alpha. The late phase (> or = 30 minutes) proceeds despite the continuous presence of anti-VLA-4 alpha. In addition, the late-phase adherence is not affected by MoAbs to LFA-1, CD44, VCAM-1, E-selectin, or L-selectin, which suggests the possible involvement of other adhesion molecules. Adherence of pre-B-lymphoblastic cells (NALM-6) to MSC is also biphasic. Integrin VLA-4 is again a major player in the early phase of pre-B-lymphoblastic cell/MSC interactions. The early phase of adherence may be important in homing of the malignant lymphoblastic cells to the MSC and the late phase in retention of malignant lymphoblastic cells in the bone marrow. 相似文献
78.
FRANK J BRANICKI ALBERT CW TING PHILIP GERTSCH HENRY H TUEN KENT-MAN CHU LOUIS WC CHOW JOHN WONG 《Journal of gastroenterology and hepatology》1998,13(Z3):S227-S231
Abstract Early surgical intervention was previously advocated in patients > 60 years with bleeding peptic ulcer presenting with haemodynamic instability or ongoing transfusion requirements. It is, however, well recognized that emergency surgical intervention with its inherent risks must be reserved for highly selected patients in whom endoscopy initially fails to control exsanquinating haemorrhage or in whom life-threatening bleeding recurs. Therapeutic endoscopy for bleeding ulcer has led to a remarkable decline in rebleeding rates, the need for emergency surgery and mortality. Octogenarians are at risk, particularly when ulcer size exceeds 2 cm. Poor surgical candidates make up two-thirds of patients with major ulcer bleeding and operation is to be avoided if at all possible. Medical therapy with proton pump inhibitor and subsequent eradication of Helicobacter pylori following endoscopic treatment has been shown to be beneficial to outcomes. Should surgery be deemed necessary, it is likely that laparoscopic techniques to control bleeding, with or without the addition of an acid-reducing procedure, will find a role in haemodynamically stable patients undergoing operation on an early elective basis. 相似文献
79.
Wilms tumor imaging: patient costs and protocol compliance 总被引:1,自引:0,他引:1
80.
A patient self-assessment tool was designed, tested, and implemented to promote cardiac-specific data collection, based on Gordon's Functional Health Patterns, to maximize patient/family involvement in determining a plan of care, and to streamline primary nurses' documentation requirements. Retrospective and concurrent chart reviews provided data for quality assurance monitoring. The results of the monitoring demonstrated that the self-assessment tool markedly improved the patient-specific data base. 相似文献