全文获取类型
收费全文 | 1544篇 |
免费 | 89篇 |
国内免费 | 113篇 |
专业分类
儿科学 | 66篇 |
妇产科学 | 14篇 |
基础医学 | 181篇 |
口腔科学 | 22篇 |
临床医学 | 174篇 |
内科学 | 400篇 |
皮肤病学 | 39篇 |
神经病学 | 106篇 |
特种医学 | 371篇 |
外国民族医学 | 6篇 |
外科学 | 51篇 |
综合类 | 42篇 |
预防医学 | 62篇 |
眼科学 | 47篇 |
药学 | 90篇 |
中国医学 | 1篇 |
肿瘤学 | 74篇 |
出版年
2023年 | 5篇 |
2022年 | 6篇 |
2021年 | 13篇 |
2020年 | 7篇 |
2019年 | 11篇 |
2018年 | 34篇 |
2017年 | 7篇 |
2016年 | 21篇 |
2015年 | 25篇 |
2014年 | 22篇 |
2013年 | 43篇 |
2012年 | 17篇 |
2011年 | 31篇 |
2010年 | 50篇 |
2009年 | 54篇 |
2008年 | 35篇 |
2007年 | 73篇 |
2006年 | 35篇 |
2005年 | 57篇 |
2004年 | 16篇 |
2003年 | 17篇 |
2002年 | 16篇 |
2001年 | 20篇 |
2000年 | 30篇 |
1999年 | 30篇 |
1998年 | 95篇 |
1997年 | 96篇 |
1996年 | 104篇 |
1995年 | 66篇 |
1994年 | 63篇 |
1993年 | 67篇 |
1992年 | 15篇 |
1991年 | 38篇 |
1990年 | 31篇 |
1989年 | 55篇 |
1988年 | 48篇 |
1987年 | 57篇 |
1986年 | 33篇 |
1985年 | 59篇 |
1984年 | 26篇 |
1983年 | 25篇 |
1982年 | 28篇 |
1981年 | 28篇 |
1980年 | 32篇 |
1979年 | 10篇 |
1978年 | 15篇 |
1977年 | 18篇 |
1976年 | 26篇 |
1975年 | 15篇 |
1959年 | 3篇 |
排序方式: 共有1746条查询结果,搜索用时 15 毫秒
71.
Stephania Donayre Pimentel Heather Adams Tamara Ellis Robin Clark Craig Sully Catherine Paré Michael JL. Sullivan 《Journal of traumatic stress》2020,33(5):731-740
Catastrophizing has been discussed as a cognitive precursor to the emergence of posttraumatic stress disorder (PTSD) symptoms following the experience of stressful events. Implicit in cognitive models of PTSD is that treatment-related reductions in catastrophizing should yield reductions in PTSD symptoms. The tenability of this prediction has yet to be tested. The present study investigated the sequential relation between changes in a specific form of catastrophizing—symptom catastrophizing—and changes in PTSD symptom severity in a sample of 73 work-disabled individuals enrolled in a 10-week behavioral activation intervention. Measures of symptom catastrophizing and PTSD symptom severity were completed at pre-, mid-, and posttreatment assessment points. Cross-sectional analyses of pretreatment data revealed that symptom catastrophizing accounted for significant variance in PTSD symptom severity, β = .40, p < .001, sr = .28 (medium effect size), even when controlling for known correlates of symptom catastrophizing, such as pain and depression. Significant reductions in symptom catastrophizing and PTSD symptoms were observed during treatment, with large effect sizes, ds = 1.42 and 0.94, respectively, ps < .001. Cross-lagged analyses revealed that early change in symptom catastrophizing predicted later change in PTSD symptoms; early changes in PTSD symptom severity did not predict later change in symptom catastrophizing. These findings are consistent with the conceptual models that posit a causal relation between catastrophizing and PTSD symptom severity. The clinical implications of the findings are discussed. 相似文献
72.
JL Adams M Murray N Patel MT Sawkin RC Boardman C Pham H Kaur D Patel JL Yager L Pontiggia J Baxter 《HIV medicine》2021,22(1):28-36
73.
巨噬细胞迁移抑制因子最初是由于能抑制体外巨噬细胞随机迁移而被发现,现在它作为一种重要的调节因子参与一系列炎症性疾病过程.我们最近发现,巨噬细胞迁移抑制因子的缺失使一些由炎症介质诱发的白细胞-内皮细胞相互作用减弱,提示巨噬细胞迁移抑制因子在炎症反应中起作用的机制之一是促进白细胞聚集.…… 相似文献
74.
Michon J; Moutel S; Barbet J; Romet-Lemonne JL; Deo YM; Fridman WH; Teillaud JL 《Blood》1995,86(3):1124-1130
Neutrophils isolated from cancer patients treated with granulocyte colony-stimulating factor (G-CSF) express high levels of Fc gamma RI. They exhibited an efficient killing of GD2+ neuroblastoma cells in the presence of an antidisialoganglioside (GD2) mouse monoclonal antibody (MoAb; 7A4, IgG3 kappa). However, this cytotoxicity was totally blocked by human monomeric IgG. In contrast, a bispecific antibody (7A4 bis 22/MDX-260), prepared by chemically linking an F(ab') fragment of 7A4 with an F(ab') fragment of an anti-Fc gamma RI MoAb, 22, which binds outside the Fc binding domain, triggered antibody-dependent cell cytotoxicity, even when neutrophils were preincubated with human monomeric IgG. F(ab')2 22 MoAb abrogated the MDX-260 killing without affecting that of 7A4. The 3G8 MoAb, directed against the Fc gamma RIII binding site, did not inhibit the cytotoxicity induced by either antibody. Thus, these results indicate that G-CSF-activated neutrophils exert their cytotoxic effect against neuroblastoma cells through Fc gamma RI and not Fc gamma RIII, and that the saturation of the high affinity Fc gamma RI by monomeric IgG can be overcome by the use of bispecific antibodies binding epitopes outside the IgG Fc gamma RI binding site. A combined administration of such bispecific antibodies and G-CSF may be, therefore, an efficient therapeutic approach to trigger tumor lysis by cytotoxic neutrophils in vivo. 相似文献
75.
76.
Topotecan, a topoisomerase I inhibitor, is active in the treatment of myelodysplastic syndrome and chronic myelomonocytic leukemia 总被引:5,自引:2,他引:5
Beran M; Kantarjian H; O'Brien S; Koller C; al-Bitar M; Arbuck S; Pierce S; Moore M; Abbruzzese JL; Andreeff M; Keating M; Estey E 《Blood》1996,88(7):2473-2479
The aim of this study was to evaluate the activity of topotecan in patients with myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML). Forty-seven patients with a diagnosis of MDS (n = 22) or CMML (n = 25) were treated. The median age was 66 years. Chromosomal abnormalities were present in 70% and thrombocytopenia less than 50 x 10(3)/microL in 51%. Evaluation of outcome and of differences among subgroups was performed according to standard methods; the criteria for response were those used for acute leukemia. Topotecan was administered as 2 mg/ m2 by continuous infusion over 24 hours daily for 5 days (10 mg/m2 per course) every 3 to 4 weeks until remission, then once every month for a maximum of 12 courses. Thirteen patients (28%) achieved a complete response (CR) and six (13%) had hematologic improvement. A CR was achieved in six of 22 patients with MDS (27%) and in seven of 25 with CMML (28%). All eight patients who presented with cytogenetic abnormalities (five chromosome 5 or 7 abnormalities) who achieved CR were cytogenetically normal in CR. Characteristics for which there was evidence of association with a higher response rate were lack of prior chemotherapy, less than 10% marrow monocytes, and absence of RAS oncogene mutations. In contrast, CR rates were similar in patients with or without abnormal karyotypes. Mucositis occurred in 64% of patients (severe in 19%) and diarrhea in 32% (severe in 13%). Febrile episodes occurred in 85% of patients and documented infections in 47%. With a median follow-up duration of 8 months, the 12-month survival rate was 38%, median survival time 10.5 months, and median remission duration 7.5 months. We conclude that topotecan has significant activity in MDS and CMML, with acceptable side effects. Future studies will investigate topotecan combined with topoisomerase II reactive agents, cytarabine, or hypomethylating agents (azacytidine and decitabine). 相似文献
77.
Cardoso AA; Schultze JL; Boussiotis VA; Freeman GJ; Seamon MJ; Laszlo S; Billet A; Sallan SE; Gribben JG; Nadler LM 《Blood》1996,88(1):41-48
Even if neoplastic cells express tumor associated antigens they still may fail to function as antigen presenting cells (APC) if they lack expression of one or more molecules critical for the induction of productive immunity. These cellular defects can be repaired by physiologic activation, transfection, or fusion of tumor cells with professional APC. Although such defects can be repaired, antitumor specific T cells may still fail to respond in vivo if they may have been tolerized. Here, human pre-B cell acute lymphoblastic leukemia (pre-B ALL) was used as a model to determine if primary human tumor cells can function as alloantigen presenting cells (alloAPC) or alternatively whether they induce anergy. In the present report, we show that pre-B cell ALL express alloantigen and adhesion molecules but uniformly lack B7-1 (CD80) and only a subset express B7-2 (CD86). Pre-B ALL cells are inefficient or ineffective alloAPC and those cases that lack expression of B7-1 and B7-2 also induce alloantigen specific T- cell unresponsiveness. Under these circumstances, T-cell unresponsiveness could be prevented by physiologic activation of tumor cells via CD40, cross-linking CD28, or signaling through the common gamma chain of the interleukin-2 receptor on T cells. Taken together, these results suggest that pre-B ALL may be incapable of inducing clinically significant T-cell-mediated antileukemia responses. This defect may be not only due to their inability to function as APC, but also due to their potential to induce tolerance. Attempts to induce clinically significant antitumor immune responses may then require not only mechanisms to repair the antigen presenting capacity of the tumor cells, but also reversal of tolerance. 相似文献
78.
Platelet-melanoma cell interaction is mediated by the glycoprotein IIb- IIIa complex 总被引:3,自引:0,他引:3
A human malignant melanoma cell line (M3Dau) was observed by electron microscopy to interact directly with human platelets and induced platelet aggregation. Fab fragments of a monoclonal antibody MoAb (LYP18), directed against the platelet glycoprotein (GP) IIb-IIIa complex, inhibited platelet-melanoma interactions and platelet-platelet aggregation. M3Dau melanoma cells bind LYP 18 and synthesize IIb-IIIa- like GPs. When the melanoma cells were preincubated with LYP 18, tumor- platelet interaction did not occur, suggesting that the interaction may be mediated by the IIb-IIIa-like GPs present on the melanoma cell surface. Glanzmann's thrombasthenic platelets, lacking GPIIb and IIIa, did not interact with melanoma cells, indicating that the platelet GPIIb-IIIa complex is also necessary for the platelet-melanoma cell interaction. This work demonstrates the importance of the IIb-IIIa-like GPs, present on M3Dau melanoma cells, in mediating tumor-platelet interactions. 相似文献
79.
Aurin tricarboxylic acid: a novel inhibitor of the association of von Willebrand factor and platelets 总被引:2,自引:1,他引:2
Shear stress activated platelets undergo aggregation in the presence of large or unusually large von Willebrand factor (vWF) multimers without the addition of ristocetin or any other exogenous chemical. This phenomenon may be analogous to the platelet aggregation that leads to thrombosis in the narrowed arteries and arterioles of patients with atherosclerosis or vasospasm. A triphenyl-methyl compound, aurin tricarboxylic acid (ATA), inhibits shear-induced, vWF-mediated platelet aggregation in platelet-rich plasma (PRP) in concentrations above 200 mumol/L and in buffer suspensions of washed platelets at a concentration of 0.1 mumol/L. In a concentration-dependent manner, ATA also inhibits ristocetin-induced, vWF-mediated platelet clumping in both fresh and formaldehyde-fixed platelet suspensions. This inhibition can be overcome by increasing the concentration of vWF, following the kinetics of first order competitive inhibition. ATA prevents the attachment to platelets of the largest vWF multimeric forms found in normal plasma and of the unusually large vWF multimers derived from endothelial cells. The rate of aggregation and degree of inhibition by ATA is not accounted for by the binding of ristocetin or calcium. Arachidonic acid- and adenosine diphosphate (ADP)-induced aggregation are not inhibited by ATA. Platelets incubated with ATA can be easily separated from the compound. However, ATA binds to large vWF multimeric forms and inhibits their ristocetin-induced interaction with platelet glycoprotein Ib. Because ATA also inhibits shear-induced, vWF-mediated platelet aggregation in vitro in the absence of ristocetin, it may be a useful prototype compound to impede the development of arterial thrombosis in vivo. 相似文献
80.
p16 gene homozygous deletions in acute lymphoblastic leukemia 总被引:15,自引:4,他引:15
Quesnel B; Preudhomme C; Philippe N; Vanrumbeke M; Dervite I; Lai JL; Bauters F; Wattel E; Fenaux P 《Blood》1995,85(3):657-663
The p16 protein is a cyclin inhibitor encoded by a gene located in 9p21, which may have antioncogenic properties, and is inactivated by homozygous p16 gene deletion or, less often, point mutation in several types of solid tumors often associated to cytogenetic evidence of 9p21 deletion. We looked for homozygous deletion and point mutation of the p16 gene in acute lymphoblastic leukemia (ALL), where 9p21 deletion or rearrangement are also nonrandom cytogenetic findings. Other hematologic malignancies including acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), chronic lymphocytic leukemia (CLL), and myeloma were also studied. Homozygous deletion of the p16 gene was seen in 9 of the 63 (14%) ALL analyzed, including 6/39 precursor B-ALL, 3/12 T-ALL, and 0/12 Burkitt's ALL. Three of the 7 ALL with 9p rearrangement (including 3 of the 5 patients where this rearrangement was clearly associated to 9p21 monosomy) had homozygous deletion compared to 5 of the 55 patients with normal 9p (the last patient with homozygous deletion was not successfully karyotyped). Single stranded conformation polymorphism analysis of exons 1 and 2 of the p16 gene was performed in 88 cases of ALL, including the 63 patients analyzed by Southern blot. Twenty-six of the cases had 9p rearrangement, associated to 9p21 monosomy in at least 12 cases. A missense point mutation, at codon 49 (nucleotide 164), was seen in only 1 of the 88 patients. No homozygous deletion and no point mutation of the p16 gene was seen in AML, MDS, CLL, and myeloma. Homozygous deletion of interferon alpha genes (situated close to p16 gene in 9p21) was seen in only 3 of the 9 ALL patients with p16 gene homozygous deletion, and none of the ALL without p16 gene homozygous deletion. Our findings suggest that homozygous deletion of the p16 gene is seen in about 15% of ALL cases, is not restricted to cases with cytogenetically detectable 9p deletion, and could have a pathogenetic role in this malignancy. On the other hand, p16 point mutations are very rare in ALL, and we found no p16 homozygous deletions or mutations in the other hematologic malignancies studied. 相似文献