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111.
Thunderclap headache: is it migraine?   总被引:1,自引:0,他引:1  
In a prospective study, 14 out of 49 patients presenting to a Regional Neurosurgical Unit with sudden headache suggestive of subarachnoid haemorrhage had normal CSF and a normal CT scan: it did not prove possible, on clinical grounds alone, to distinguish these from those that had bled. We have now followed all these patients for a minimum of 18 months. Only one has had no further headache, 4 have had musculoskeletal pain, 5 psychogenic pain, and 4 migraine type symptoms. None went on to have an unequivocal subarachnoid haemorrhage, and we conclude that angiography cannot be justified in patients with this type of "thunderclap headache".  相似文献   
112.
Kingma  DW; Weiss  WB; Jaffe  ES; Kumar  S; Frekko  K; Raffeld  M 《Blood》1996,88(1):242-251
LMP-1, an Epstein-Barr viral (EBV) latency protein, is considered a viral oncogene because of its ability to transform rodent fibroblasts in vivo and render them tumorigenic in nude mice. In human B cells, EBV LMP-1 induces DNA synthesis and abrogates apoptosis. LMP-1 is expressed in EBV-transformed lymphoblastoid cell lines, nasopharyngeal carcinoma (NPC), a subset of Hodgkin's disease (HD), and in EBV-associated lymphoproliferative disorders (EBV-LPDs). Recently, focused deletions near the 3' end of the LMP-1 gene (del-LMP-1, amino acids 346-355), in a region functionally related to the half-life to the LMP-1 protein, have been reported frequently in human immunodeficiency virus (HIV)- associated HD (100%) and EBV+ Malaysian and Danish peripheral T-cell lymphomas (100%, 61% respectively), but less frequently in cases of HD not associated with HIV (28%, 33%) and infectious mononucleosis (33%). To further investigate the potential relationship of del-LMP-1 to EBV- LPDs associated with immunosuppression or immunodeficiency, we studied 39 EBV-associated lymphoproliferations (10 benign, 29 malignant) from four distinct clinical settings: posttransplant (4 malignant, 1 reactive); HIV+ (18 malignant, 2 reactive); nonimmunodeficiency malignant lymphoma (ML) (7 cases); and sporadic EBV infection with lymphoid hyperplasia (7 cases). The presence of EBV within lymphoid cells was confirmed by EBV EBER1 RNA in situ hybridization or by polymerase chain reaction (PCR) analysis. EBV strain type and LMP-1 deletion status were determined by PCR. EBV strain types segregated into two distinct distributions: HIV+ (9 A; 11 B) and non-HIV (19 A, 0 B), consistent with previous reports. Overall, del-LMP-1 were found in 1 of 5 (20%) Burkitt lymphomas (BL); 17 of 24 (71%) aggressive non- Hodgkin's lymphoma (agg-NHL), and 2 of 10 (20%) reactive lymphoid proliferations. Of the agg-NHLs, del-LMP-1 were present in 4 of 4 PT-ML (100%); 10 of 15 HIV+ ML (67%); and 3 of 5 nonimmunodeficiency malignant lymphoma (ML, 60%). A total of 2 of 7 (28%) sporadic EBV- associated lymphoid hyperplasias contained a del-LMP-1. All del-LMP-1 were identical by DNA sequence analysis. No correlation was identified between the presence of del-LMP-1 and the EBV strain type observed. The high incidence of del-LMP-1 observed in agg-NHLs (71%), in contrast to the relatively low incidence observed in reactive lymphoid proliferations (28%), suggests that the deleted form may be preferentially selected in lymphomatous processes. All posttransplant agg-NHLs contained a del-LMP-1, and a similar frequency of del-LMP-1 was observed in both HIV-associated ML (66%) and nonimmunodeficiency ML (60%), suggesting that impairment of immune function alone is not a requirement for the expansion of malignant cells infected by EBV stains containing the deleted LMP-1 gene.  相似文献   
113.
We identified eight cases of T-cell lymphoma with evidence of a gamma delta phenotype over a 13-year period. Seven of these cases conformed to a distinct clinicopathologic entity of hepatosplenic gamma delta T- cell lymphoma. Nearly all of these patients were young adult males (five of seven), with a median age at presentation of 20 years. They presented with marked hepatosplenomegaly, without lymphadenopathy or significant peripheral blood lymphocytosis. Thrombocytopenia was seen in all patients, and five of seven were mildly anemic. The clinical course was aggressive, and despite multiagent chemotherapy, the median survival duration was less than 1 year. The morphologic findings were uniform; a monomorphic population of medium-sized lymphoid cells with moderately clumped chromatin and a rim of pale cytoplasm infiltrated the sinusoids of the spleen, liver, and bone marrow. The cells had a characteristic immunophenotype: CD2+, CD3+, CD4-, CD5-, CD7+, CD16+, CD57-, CD25-, T-cell receptor (TCR)delta +, beta F1-. CD8 was positive in four of seven cases tested, and CD56 was positive in five of six. All cases expressed the cytotoxic granule-associated protein, TIA1, but perforin was detected in only one case. All cases with assessable DNA had a TCR gamma gene rearrangement, and lacked Epstein-Barr virus sequences. Isochromosome 7q was identified in two cases with cytogenetic information. The one case of cutaneous gamma delta T-cell lymphoma differed in its clinical manifestations, histologic appearance, and immunophenotype. We conclude that hepatosplenic gamma delta T-cell lymphoma is a distinct clinicopathologic entity derived from cytotoxic gamma delta T cells, and should be distinguished from other lymphomas of T-cell and natural-killer cell (NK)-like T-cell derivation.  相似文献   
114.
Tomonaga  M; Gasson  JC; Quan  SG; Golde  DW 《Blood》1986,67(5):1433-1441
Recent observations indicating that the HL-60 human acute promyelocytic leukemia cell line contains a minor eosinophil population in addition to neutrophil and mononuclear phagocyte progenitors suggest the multipotentiality of HL-60 stem cells. In order to clarify multilineage differentiation and commitment to single-lineage progenitors we analyzed HL-60 colonies formed in methylcellulose. In an HL-60 parent line with a relatively high eosinophil content (5.5%), 36% of the spontaneous colonies consisted partly or wholly of eosinophilic cells. After two rounds of subcloning in methylcellulose, two eosinophilic sublines and two neutrophilic sublines were established. These lines have been in continuous liquid culture for more than four months, and they show stable single-lineage differentiation. Purified biosynthetic GM-CSF, which stimulates normal CFU-GM and CFU-EO, induced monocytic differentiation but no eosinophilic differentiation in the neutrophilic sublines and no neutrophilic or monocytic differentiation in the eosinophilic sublines. These observations indicate that HL-60 stem cells are multipotent and capable of spontaneous commitment to single- lineage progenitors. The eosinophilic HL-60 sublines should facilitate studies on the production and function of human eosinophils and the single-lineage sublines will allow further analysis of leukemic cell differentiation and stem cell commitment.  相似文献   
115.
Slapak  CA; Mizunuma  N; Kufe  DW 《Blood》1994,84(9):3113-3121
Drug-resistant sublines of the human U-937 myeloid leukemia cell line were selected in doxorubicin concentrations of 10, 40, and 200 ng/mL (designated U-A10, U-A40, and U-A200, respectively). Northern blot analysis showed overexpression of the multidrug resistance-associated protein (MRP) gene, but not MDR1, in U-A10 cells as compared with parental U-937 cells. Prolonged passage of U-A10 cells in 10 ng/mL of doxorubicin had little effect on MRP RNA levels, but increased MDR1 expression. The U-A40 and U-A200 cells, derived by selection of U-A10 cells, showed high levels of both MRP and MDR1 expression. None of the drug-resistant cell lines showed MRP or MDR1 gene amplification as judged by Southern blot analysis. U-A10 cells exhibited minimal decreased net accumulation of anthracycline, whereas U-A40 and U-A200 cells showed more significantly decreased drug accumulation as compared with U-937 cells. Subcellular anthracycline accumulation in U-937 cells as determined by fluorescence microscopy showed daunorubicin fluorescence predominately in the nucleus. However, the drug-resistant cell lines showed minimal nuclear drug accumulation with marked redistribution of drug into a vesicular compartment. Treatment with sodium azide/2-deoxyglucose, 2,4-dinitrophenol, or monensin, but not verapamil, abolished the vesicular accumulation. These studies in doxorubicin-selected U-937 cells indicate that induction of MRP overexpression occurs before that for the MDR1 gene. In addition, the drug-resistant cells possess an energy-dependent redistribution of anthracyclines into a nonnuclear vesicular compartment.  相似文献   
116.
Blood warming: current applications and techniques   总被引:5,自引:0,他引:5  
Active blood warming is a recent practice and arises out of conflicting needs. On the one hand, the safety and preservation of blood require refrigerated storage and delivery up to the moment of transfusion. On the other hand, modern methods of very rapid transfusion in resuscitation would cause clinically dangerous hypothermia if unmodified, ice-cold blood were to be so transfused. These needs must be reconciled in the interest of adequate patient care--hence the need for blood warming. Nevertheless, blood warming creates risks of its own and should not be used without justifying clinical indications. Within limits that extend somewhat above normal body temperature, the application of heat does no harm to stored RBC, a fact that is not reflected in current standards for blood warmers. Bearing in mind the human tendency to "stretch" standards and the fallibility of mechanical devices, caution is always wise. But perhaps the time has come for reconsideration of the present upper limit of 38 degrees C. Many varieties of blood warmers are available in the US, but none at this time is based on electromagnetic activity. The most common systems now in use are in-line warmers, most of which are not adequate for the type of rapid-transfusion systems currently available. Countercurrent in-line blood warmers and the method of rapid warm saline admixture can both be used successfully for rapid, massive transfusions. Blood warming is seldom necessary or desirable for elective transfusions at conventional rates, even for patients with cold autoagglutinins.  相似文献   
117.
Thrombopoietin (TPO) is a recently characterized growth and differentiation factor for megakaryocytes and platelets that exerts its effects via the receptor, c-MpI. This receptor is a member of the hematopoietin receptor superfamily and is essential for megakaryocyte maturation; however, the molecular mechanisms of TPO and c-MpI action have not been elucidated. Recently, the Janus kinases have emerged as important elements in signaling via this family of receptors. In this report, we show that, in the M07e megakaryocytic cell line, which expresses c-MpI and proliferates in response to TPO, TPO induces phosphorylation of a number of substrates between 80 and 140 kD. Specifically, we show that stimulation with TPO induces the rapid tyrosine phosphorylation of a 130-kD protein that we identify as the Janus kinase, JAK2. However, no detectable tyrosine phosphorylation of JAK1, JAK3, or TYK2 was observed. TPO also induced activation of JAK2 phosphotransferase activity in vitro. Taken together, these data indicate that JAK2 likely plays a key role in TPO-mediated signal transduction.  相似文献   
118.
Ware  J; Davis  L; Frazier  D; Bajaj  SP; Stafford  DW 《Blood》1988,72(2):820-822
DNA sequence analysis of the gene coding for the variant protein, factor IXLong Beach (FIXLB), has identified a transition mutation in an otherwise normal factor IX (FIX) gene. Genomic DNA clones spanning 35 kilobase (kb) pairs of the FIXLB gene were isolated. A gene analysis strategy that specifically characterized exons and their flanking intron sequences predicted the entire amino acid sequence of FIXLB. A thymine to cytosine transition causes the substitution of a threonine codon (ACA) for an isoleucine codon (ATA) in exon VIII of the FIXLB gene. This mutation results in an amino acid substitution at residue 397 of the FIX zymogen and the phenotypic display of hemophilia-B. Previous studies revealed that activated purified FIXLB (FIXaLB) had normal Ca2+, phospholipid, and factor VIIIa binding characteristics. However, FIXaLB activated factor X or factor VII (with their cofactors Ca2+ and phospholipid) at significantly reduced rates, suggesting that the defect in FIXaLB lies near or within the catalytic triad of the FIX heavy chain. Identification of an amino acid substitution near the carboxy-terminus of the FIXaLB heavy chain supports the earlier characterization of this variant protein. Moreover, our data identify a residue in the catalytic domain of FIXa essential for normal function.  相似文献   
119.
Aboud  M; Golde  DW; Bersch  N; Rosenblatt  JD; Chen  IS 《Blood》1987,70(2):432-436
We report here the development of a rapid and quantitative method for measuring in vitro T cell transformation by human T cell leukemia viruses type I (HTLV-I) and type II (HTLV-II). This method is based on our finding that cocultivation of lethally irradiated HTLV-producing cells with peripheral blood lymphocytes (PBLs) preactivated for 24 hours with phytohemagglutinin and interleukin-2 (IL-2) induces colony formation in methylcellulose-containing medium. Colonies of about 200 cells can be clearly distinguished from background aggregates within four to six days after cocultivation. These colonies gradually increase in size and reach 300 to 1,000 cells within 14 days after cocultivation. Cells of these colonies were infected, as evidenced by expression of viral p19 antigen and the presence of HTLV proviral sequences. These cells proved to be transformed in terms of IL-2- independent continuous growth in liquid medium. Colony formation was found to depend in a linear fashion upon the percentage of the infected cells present in the irradiated cell population and is sufficiently sensitive to detect as few as 1% of virus-producing cells.  相似文献   
120.
Chesler  L; Golde  DW; Bersch  N; Johnson  MD 《Blood》1995,86(12):4506-4515
Tissue inhibitor of metalloproteinases-1 (TIMP-1), the major physiological matrix metalloproteinase inhibitor and a potent antimetastatic factor, also stimulates the growth of erythroid progenitors (erythroid-potentiating activity). We analyzed the relationship between the growth factor activity and protease inhibition by preparing purified TIMP-1 "knockout" proteins lacking in vitro antiproteolytic activity. The growth-stimulatory effect of these N- terminal TIMP-1 point mutants, as tested in an in vitro assay using erythroid precursors (erythroid burst-forming units) was equal to that of unmutated TIMP-1. A fully antiproteolytic C-terminal TIMP-1 truncation also stimulated growth in the erythroid burst-forming unit assay. The results indicate that the influence of TIMP-1 on erythroid precursor growth is independent of its ability to inhibit metalloproteinases. TIMP-1 is analogous to proteins that have both proteolytic and growth factor activity, such as plasmin, thrombin, and urokinase. However, TIMP-1 is novel in this regard because it is a metalloproteinase inhibitor. We show that the antiproteolytic and growth factor activities of the TIMP-1 molecule are physically and functionally distinct.  相似文献   
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