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排序方式: 共有251条查询结果,搜索用时 31 毫秒
51.
Dale DC; Bonilla MA; Davis MW; Nakanishi AM; Hammond WP; Kurtzberg J; Wang W; Jakubowski A; Winton E; Lalezari P 《Blood》1993,81(10):2496-2502
Patients with idiopathic, cyclic, and congenital neutropenia have recurrent severe bacterial infections. One hundred twenty-three patients with recurrent infections and severe chronic neutropenia (absolute neutrophil count < 0.5 x 10(9)/L) due to these diseases were enrolled in this multicenter phase III trial. They were randomized to either immediately beginning recombinant human granulocyte colony- stimulating factor (filgrastim) (3.45 to 11.50 micrograms/kg/d, subcutaneously) or entering a 4-month observation period followed by filgrastim administration. Blood neutrophil counts, bone marrow (BM) cell histology, and incidence and duration of infection-related events were monitored. Of the 123 patients enrolled, 120 received filgrastim. On therapy, 108 patients had a median absolute neutrophil count of > or = 1.5 x 10(9)/L. Examination of BM aspirates showed increased proportions of maturing neutrophils. Infection-related events were significantly decreased (P < .05) with approximately 50% reduction in the incidence and duration of infection-related events and almost 70% reduction in duration of antibiotic use. Asymptomatic splenic enlargement occurred frequently; adverse events frequently reported were bone pain, headache, and rash, which were generally mild and easily manageable. These data indicate that treatment of patients with severe chronic neutropenia with filgrastim results in a stimulation of BM production and maturation of neutrophils, an increase in circulating neutrophils, and a reduction in infection-related events. 相似文献
52.
Dercksen MW; Gerritsen WR; Rodenhuis S; Dirkson MK; Slaper-Cortenbach IC; Schaasberg WP; Pinedo HM; von dem Borne AE; van der Schoot CE 《Blood》1995,85(11):3313-3319
Adhesion molecules play a role in the migration of hematopoietic progenitor cells and regulation of hematopoiesis. To study whether the mobilization process is associated with changes in expression of adhesion molecules, the expression of CD31, CD44, L-selectin, sialyl Lewisx, beta 1 integrins very late antigen 4 (VLA-4) and VLA-5, and beta 2 integrins lymphocyte function-associated 1 and Mac-1 was measured on either bone marrow (BM) CD34+ cells or on peripheral blood CD34+ cells mobilized with a combination of granulocyte colony- stimulating factor (G-CSF) and chemotherapy. beta 1 integrin VLA-4 was expressed at a significantly lower concentration on peripheral blood progenitor cells than on BM CD34+ cells, procured either during steady- state hematopoiesis or at the time of leukocytapheresis. No differences in the level of expression were found for the other adhesion molecules. To obtain insight in which adhesion molecules may participate in the homing of peripheral blood stem cells (PBSCs), the number of CD34+ cells expressing these adhesion molecules present in leukocytapheresis material was quantified and correlated with hematopoietic recovery after intensive chemotherapy in 27 patients. The number of CD34+ cells in the subset defined by L-selectin expression correlated significantly better with time to platelet recovery after PBSC transplantation (r = - .86) than did the total number of CD34+ cells (r = -.55). Statistical analysis of the relationship between the number of CD34+L-selectin+ cells and platelet recovery resulted in a threshold value for rapid platelet recovery of 2.1 x 10(6) CD34+ L-selectin+ cells/kg. A rapid platelet recovery (< or = 14 days) was observed in 13 of 15 patients who received > or = 2.1 x 10(6) CD34+ L-selectin+ cells/kg (median, 11 days; range, 7 to 16 days), whereas 10 of 12 patients who received less double positive cells had a relative slow platelet recovery (median, 20 days; range, 13 to 37 days). The L-selectin+ subpopulation of CD34+ cells also correlated better with time to neutrophil recovery (r = - .70) than did the total number of reinfused CD34+ cells (r = -.51). However, this latter difference failed to reach statistical significance. This study suggests that L-selectin is involved in the homing of CD34+ cells after PBSC transplantation. 相似文献
53.
Characterization of endogenous cytokine concentrations after high-dose chemotherapy with autologous bone marrow support 总被引:3,自引:0,他引:3
Endogenous cytokines are thought to mediate numerous biologic processes and may account for some adverse effects experienced following the administration of recombinant proteins. This study describes the pattern of endogenous cytokine exposure following high-dose chemotherapy. Blood concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), macrophage colony-stimulating factor (M-CSF), and erythropoietin (EPO) were measured by enzyme-linked immunosorbent assay (ELISA) methods in 68 patients receiving the same ablative chemotherapy regimen (cyclophosphamide, cisplatin, carmustine). Patients were grouped according to cellular support (autologous bone marrow [BM] CSF-primed peripheral blood progenitor cells [PBPCs]) and prescribed growth factor (recombinant human granulocyte or granulocyte-macrophage colony-stimulating factor [rHuG- CSF or rHuGM-CSF]). Leukocyte reconstitution was most accelerated in the groups treated with PBPCs and rHuG-CSF. IL-6, M-CSF, and TNF-alpha concentrations were higher in the groups treated with rHuGM-CSF and without PBPCs. Maximal endogenous cytokine concentrations occurred approximately 12 days after BM reinfusion. High concentrations of EPO occurred in patients experiencing significant hypotension despite routine transfusions for hematocrit < 42%. High M-CSF and IL-6 levels were associated with increased platelet transfusion requirements. Concentrations of all four cytokines were significantly higher in patients experiencing renal or hepatic toxicity, with elevations occurring in a predictable sequence and M-CSF elevations occurring first. This report shows that endogenous cytokine concentrations may be influenced by either cellular or CSF support and are associated with differences in platelet reconstitution and organ toxicity. 相似文献
54.
Op den Kamp CM Langen RC Minnaard R Kelders MC Snepvangers FJ Hesselink MK Dingemans AC Schols AM 《Lung cancer (Amsterdam, Netherlands)》2012,76(1):112-117
Cachexia is a prevalent phenomenon of non-small cell lung cancer (NSCLC) which is responsible for increased mortality and deterioration of physical performance. Preclinical research indicates that systemic inflammation induces cachexia-related muscle wasting through muscular Nuclear Factor-kappa B (NF-κB) signaling and subsequent ubiquitin proteasome system (UPS)-mediated proteolysis. As these pathways could be a target for early intervention strategies, it needs to be elucidated whether increased activation of these pathways is already present in early stage NSCLC cachexia. The aim of the present study was therefore to assess muscular NF-κB and UPS activation in patients with NSCLC pre-cachexia. Sixteen patients with newly diagnosed stages I-III NSCLC having <10% weight loss and ten healthy controls were studied. Body composition, systemic inflammation and exercise capacity were assessed in all subjects and NF-κB and UPS activity in vastus lateralis muscle biopsies in a subset. Patients showed increased plasma levels of C-reactive protein (CRP) (P<0.001), soluble Tumor Necrosis Factor receptor 1 (sTNF-R1) (P<0.05), fibrinogen (P<0.001) and decreased levels of albumin (P<0.001). No changes in fat free body mass or skeletal muscle NF-κB and UPS activity were observed, while peak oxygen consumption ( [Formula: see text] ) was significantly decreased in patients compared with healthy controls. In conclusion, this exploratory study demonstrates significantly reduced exercise capacity in NSCLC pre-cachexia despite maintenance of muscle mass and unaltered indices of UPS activation. The absence of muscular NF-κB-dependent inflammatory signaling supports the notion that transition of systemic to local inflammation is required to initiate UPS-dependent muscle wasting characteristic for (experimental) cachexia. 相似文献
55.
Mai WP 《中国医药工业杂志》2009,40(4)
空间位阻、对空气稳定的单氧氯化膦与Pd2(dba)3反应原位形成复合物,可促进芳基硼酸与芳基卤的Suzuki交叉偶联反应。芳基卤上有吸电子基时反应性更高,羰基及氰基无需保护。13例收率66%~93%。 相似文献
56.
目的:研究慢性肝炎患者HBV-DNA水平与病情变化的关系. 方法:采用荧光标记定量PCR的方法,测定慢性乙型肝炎急性发作患者(HBeAg阳性45例,抗HBe阳性30例)其活动期和恢复期的血清HBV-DNA含量. 结果:HBeAg阳性组血清HBV-DNA含量(Logarrithm copy/mL)在活动期显著高于恢复期[(10.2±1.6) vs (5.3±2.1), P<0.05],抗-HBe阳性组血清HBV-DNA含量(Logarrithm copy/mL)在活动期显著高于恢复期[(7.6±1.3) vs (4.0±2.0), P<0.05]. 另外,活动期血清HBV-DNA含量(Logarrithm copy/mL)在HBeAg阳性组显著高于抗HBe阳性组[(10.2±1.6) vs (7.6±1.3), P<0.05]. 血清HBV-DNA水平与丙氨酸转氨酶(ALT)、门冬氨酸转氨酶(AST)及总胆红素(T-BLLI)之间无相关性. 结论:HBV-DNA复制水平与慢性乙型病毒性肝炎的活动密切相关. 相似文献
57.
Serum, plasma and paraffin-embedded tissues as sources of DNA for studying cancer susceptibility genes 总被引:1,自引:1,他引:1
The ability to isolate DNA from archived human serum, plasma and
paraffin-embedded human tissues enhances opportunities to study breast,
lung and other cancer risk factors. We report herein a simple and fast
protocol for the extraction of genomic DNA from these sources. Using a
phenol-based extraction method, the recovery for DNA is quantitative and
reproducible. DNA yields in serum (250 microl) were between 162 and 1060 ng
(n = 18 subjects), in plasma (250 microl) were between 165 and 375 ng (n =
5 subjects) and in embedded tissues (5-microm thick sections for ethanol
fixed, and between 5- and 20-microm sections for formaldehyde fixation)
were between 1 microg and 11.7 microg (n = 32 subjects). The extraction
method was combined with newly designed PCR- based assays for cancer
susceptibility marker genes such as CYP1A1 (exon 7), CYP2E1 (Dra1, Rsa1),
GSTM1 and NAT2 [NAT2*5A (C481T), NAT2*6A (G590A), NAT2*7A (G857A)].
Genotyping results from the serum and paraffin-embedded tissues compared
favorably to results from archived freshly frozen tissues, where
concordance was 98% for serum, 100% for ethanol-fixed embedded tissues, and
97% for formaldehyde-fixed and paraffin-embedded tissues. This facile
method will allow for the use of archived tissue samples of prospective
cohort and other studies where intact DNA was not previously available.
相似文献
58.
Mutation analysis of the Smad2 gene in human colon cancers using genomic DNA and intron primers 总被引:2,自引:0,他引:2
Takenoshita S; Tani M; Mogi A; Nagashima M; Nagamachi Y; Bennett WP; Hagiwara K; Harris CC; Yokota J 《Carcinogenesis》1998,19(5):803-807
In mammals, one of the Mad homologues, Smad2, was reported to be a mediator
of TGF-beta signaling, and was found mutated in some cases of colon and
lung cancers. To extend the analysis of this gene, we previously
investigated the genomic organization of the human Smad2 gene and defined
the structure of 12 exons and flanking introns. In this study, we designed
11 sets of intron-based primers to examine the entire coding region of the
Smad2 gene. By the PCR-SSCP method using these primers, we screened genomic
DNA sequences of colorectal cancers for mutations of the Smad2 gene. Though
there was no mutation within all exons of the Smad2 gene, two of 60
sporadic colorectal cancers displayed deletions in the polypyrimidine tract
preceding exon 4. Deletions of this region were also detected in colon
cancer cell lines, and were clustered within cells exhibiting
microsatellite instability. Deletions in the polypyrimidine tract had
various effects on pre-mRNA splicing, but had no effect on the splicing of
the Smad2 gene in these cases. However, our data support the idea that the
polypyrimidine tract in the splicing acceptor site is a target of mutations
in mismatch repair-deficient tumors.
相似文献
59.
Short-term adaptation of the cervico-ocular reflex 总被引:2,自引:0,他引:2
Rijkaart DC van der Geest JN Kelders WP de Zeeuw CI Frens MA 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2004,156(1):124-128
Inhibition of return (IOR) refers to slowed responses to targets presented at the same location as a preceding stimulus. IOR is typically investigated using a cue-target design, in which subjects respond only to the second stimulus of a pair. In such tasks, the measurement of true IOR may be confounded by the effect of non-ocular response inhibition, because the participant must suppress any tendency to respond (e.g. key press) to the first stimulus. This confound may be eliminated using a target-target design, in which responses are made to both stimuli. We assessed the contribution of non-ocular response inhibition to visual IOR, measured in a cue-target task, by testing participants on both cue-target and target-target detection tasks, with identical timings and stimuli. Significant IOR was obtained in both tasks but, at a stimulus onset asynchrony (SOA) of 1,400 ms, IOR magnitude was significantly greater in the cue-target condition than in the target-target condition. However, at an SOA of 1,800 ms, there was no significant difference in the magnitude of IOR between the two tasks. Thus, a proportion of the total IOR effect observed in visual cue-target tasks can be attributed to non-ocular response inhibition, but this process appears to decay more rapidly than does true IOR, having dissipated by 1,800 ms following cue onset. 相似文献
60.