全文获取类型
收费全文 | 1674篇 |
免费 | 115篇 |
国内免费 | 16篇 |
专业分类
耳鼻咽喉 | 49篇 |
儿科学 | 52篇 |
妇产科学 | 9篇 |
基础医学 | 179篇 |
口腔科学 | 17篇 |
临床医学 | 157篇 |
内科学 | 264篇 |
皮肤病学 | 16篇 |
神经病学 | 292篇 |
特种医学 | 247篇 |
外科学 | 233篇 |
综合类 | 53篇 |
预防医学 | 93篇 |
眼科学 | 19篇 |
药学 | 74篇 |
中国医学 | 2篇 |
肿瘤学 | 49篇 |
出版年
2021年 | 13篇 |
2020年 | 16篇 |
2019年 | 7篇 |
2018年 | 16篇 |
2017年 | 21篇 |
2016年 | 25篇 |
2015年 | 15篇 |
2014年 | 25篇 |
2013年 | 42篇 |
2012年 | 41篇 |
2011年 | 38篇 |
2010年 | 46篇 |
2009年 | 60篇 |
2008年 | 60篇 |
2007年 | 68篇 |
2006年 | 70篇 |
2005年 | 63篇 |
2004年 | 57篇 |
2003年 | 63篇 |
2002年 | 51篇 |
2001年 | 47篇 |
2000年 | 55篇 |
1999年 | 54篇 |
1998年 | 53篇 |
1997年 | 56篇 |
1996年 | 44篇 |
1995年 | 31篇 |
1994年 | 46篇 |
1993年 | 32篇 |
1992年 | 31篇 |
1991年 | 36篇 |
1990年 | 33篇 |
1989年 | 49篇 |
1988年 | 42篇 |
1987年 | 42篇 |
1986年 | 45篇 |
1985年 | 41篇 |
1984年 | 33篇 |
1983年 | 22篇 |
1982年 | 25篇 |
1981年 | 29篇 |
1980年 | 8篇 |
1979年 | 10篇 |
1978年 | 15篇 |
1977年 | 12篇 |
1976年 | 16篇 |
1975年 | 16篇 |
1974年 | 11篇 |
1934年 | 6篇 |
1932年 | 5篇 |
排序方式: 共有1805条查询结果,搜索用时 290 毫秒
41.
Graziani G; Pasqualetti D; Lopez M; D'Onofrio C; Testi AM; Mandelli F; Gallo RC; Bonmassar E 《Blood》1987,69(4):1175-1181
Peripheral mononuclear cells (MNC) collected from 12 healthy donors and 44 leukemic patients at various stages of the disease were tested for natural killer (NK) activity and for their susceptibility to HTLV-I infection in vitro, measured in terms of percentage of p19 positive cells. MNC from leukemic donors at any stage of leukemia (ie, onset or relapse, ON/REL; complete remission or off-therapy, CR/OT donors) were highly susceptible to HTLV-I infection. This was true for acute leukemias of lymphoblastic (ALL) or nonlymphoblastic (ANLL) type. MNC of ON/REL patients were more susceptible to HTLV-I than those of CR/OT donors. In addition, leukemic blasts were more rapidly infected (ie, within five to seven days) than the HTLV-I-susceptible normal cord- blood lymphocytes. However, the presence of circulating blasts was not essential to virus susceptibility, since CR/OT MNC, presumably free of leukemic blasts, were still more susceptible to HTLV-I than normal cells. Basal NK function of MNC from leukemic patients was significantly lower than that detectable in healthy controls. However, no correlation was found between susceptibility to HTLV-I infection and NK activity. 相似文献
42.
43.
Nadra I Boccaccini AR Philippidis P Whelan LC McCarthy GM Haskard DO Landis RC 《Atherosclerosis》2008,196(1):98-105
Macrophages may promote a vicious cycle of inflammation and calcification in the vessel wall by ingesting neointimal calcific deposits (predominantly hydroxyapatite) and secreting tumor necrosis factor (TNF)alpha, itself a vascular calcifying agent. Here we have investigated whether particle size affects the proinflammatory potential of hydroxyapatite crystals in vitro and whether the nuclear factor (NF)-kappaB pathway plays a role in the macrophage TNFalpha response. The particle size and nano-topography of nine different crystal preparations was analyzed by X-ray diffraction, Raman spectroscopy, scanning electron microscopy and gas sorbtion analysis. Macrophage TNFalpha secretion was inversely related to hydroxyapatite particle size (P=0.011, Spearman rank correlation test) and surface pore size (P=0.014). A necessary role for the NF-kappaB pathway was demonstrated by time-dependent I kappaB alpha degradation and sensitivity to inhibitors of I kappaB alpha degradation. To test whether smaller particles were intrinsically more bioactive, their mitogenic activity on fibroblast proliferation was examined. This showed close correlation between TNFalpha secretion and crystal-induced fibroblast proliferation (P=0.007). In conclusion, the ability of hydroxyapatite crystals to stimulate macrophage TNFalpha secretion depends on NF-kappaB activation and is inversely related to particle and pore size, with crystals of 1-2 microm diameter and pore size of 10-50 A the most bioactive. Microscopic calcific deposits in early stages of atherosclerosis may therefore pose a greater inflammatory risk to the plaque than macroscopically or radiologically visible deposits in more advanced lesions. 相似文献
44.
Suppression of apoptosis in hematopoietic factor-dependent progenitor cell lines by expression of the FAC gene 总被引:2,自引:5,他引:2
Fanconi anemia (FA) is a genetically heterogeneous, inherited blood disorder characterized by bone marrow failure, congenital malformations, and a predisposition to leukemias. Because FA cells are hypersensitive to DNA cross-linking agents and have chromosomal instability, FA has been viewed as a disorder of DNA repair. However, the exact cellular defect in FA cells has not been identified. Sequence analysis of the gene defective in group C patients (FAC) has shown no significant homologies to other known genes. The FAC protein has been localized to the cytoplasm, indicating that FAC may either play an indirect role in DNA repair or is involved in a different cellular pathway. Recent evidence has indicated that FA cells may be predisposed to apoptosis, especially after treatment with DNA cross-linking agents. The demonstration that genes can suppress apoptosis has been accomplished by overexpression of such genes in growth factor-dependent cell lines that die by apoptosis after factor withdrawal. Using retroviral-mediated gene transfer, we present evidence that expression of FAC in the hematopoietic factor-dependent progenitor cell lines 32D and MO7e can suppress apoptosis induced by growth factor withdrawal. Flow cytometry and morphologic analysis of propidium iodide stained cells showed significantly lower levels of apoptosis in FAC-retroviral transduced cells after growth factor deprivation. Expression of FAC in both cell lines promoted increased viability rather than proliferation, which is consistent with other apoptosis-inhibiting genes such as Bcl- 2. These findings imply that FAC may act as a mediator of an apoptotic pathway initiated by growth factor withdrawal. Furthermore, the congenital malformations and hematologic abnormalities characterizing FA may be related to an increased predisposition of FA progenitor cells to undergo apoptosis, particularly in the absence of extracellular signals. 相似文献
45.
Factors that affect human hemopoiesis are produced by T-cell growth factor dependent and independent cultured T-cell leukemia-lymphoma cells 总被引:3,自引:0,他引:3
Some laboratory results and clinical situations suggest that human T cells may be important in the regulation of growth of hematopoietic cells. Since the discovery of T-cell growth factor (TCGF), systems are now available for the long-term specific in vitro propagation of mature normal or neoplastic human T cells, providing an opportunity to study the influence of T cells on hematopoiesis. Recently, 24 cell lines from patients with cutaneous T-cell lymphoma (CTCL) and T-cell acute lymphoblastic leukemia (T-ALL) were grown with TCGF and then assessed for release of humoral factors that affect hematopoiesis. Conditioned media (CM) from these cell lines were tested for erythroid burst- promoting activity (BPA) and granulocyte colony-stimulating activity (CSA). BPA was detected in CM from 3/6 cultures of T-ALL patients and 4/6 CTCL cultures. CSA was found in the CM from 6/8 cultures of T-ALL patients, 7/12 CTCL cultures, and 3/4 CTCL cell lines that become independent of exogenous TCGF for growth. The CSA from several of the neoplastic T-cell cultures stimulated high levels of eosinophil colonies, a possible source of the eosinophilia seen in these patients. The ability of continuously proliferating human T lymphocytes, which retain functional specificity and responsiveness to normal humoral regulation, to produce factors that directly or indirectly stimulate myeloid and erythroid colony formation lends further credence to the role of T lymphocytes in regulating hematopoiesis. 相似文献
46.
47.
Effect of empiric antiarrhythmic therapy in resuscitated out-of-hospital cardiac arrest victims with coronary artery disease 总被引:1,自引:0,他引:1
A R Moosvi S Goldstein S VanderBrug Medendorp J R Landis R A Wolfe R Leighton G Ritter C M Vasu A Acheson 《The American journal of cardiology》1990,65(18):1192-1197
The effect of empiric antiarrhythmic therapy with quinidine and procainamide on long-term mortality was examined in 209 patients with coronary artery disease resuscitated after out-of-hospital cardiac arrest. The antiarrhythmic agent used was determined by the patient's private physician without knowledge of the study ambulatory electrocardiogram. Of the 209 patients, procainamide was prescribed in 45 (22%), quinidine in 48 (23%) and no antiarrhythmic therapy in 116 (55%). Digoxin therapy was initiated in 101 patients. The 2-year total survival rate for the quinidine, procainamide and nontreated patients was 61, 57 and 71% (p less than 0.05), and for sudden death was 69, 69 and 89% (p less than 0.01), respectively. These observations suggest that empiric antiarrhythmic therapy in survivors of out-of-hospital cardiac arrest did not affect total mortality and was associated with an increased frequency of sudden death. 相似文献
48.
Guida Landouré Peng‐Peng Zhu Charles M. Lourenço Janel O. Johnson Camilo Toro Katherine V. Bricceno Carlo Rinaldi Katherine G. Meilleur Modibo Sangaré Oumarou Diallo Tyler M. Pierson Hiroyuki Ishiura Shoji Tsuji Nichole Hein John K. Fink Marion Stoll Garth Nicholson Michael A. Gonzalez Fiorella Speziani Alexandra Dürr Giovanni Stevanin Leslie G. Biesecker for the NIH Intramural Sequencing Center John Accardi Dennis M. D. Landis William A. Gahl Bryan J. Traynor Wilson Marques Jr Stephan Züchner Craig Blackstone Kenneth H. Fischbeck Barrington G. Burnett 《Human mutation》2013,34(10):1357-1360
We report here the genetic basis for a form of progressive hereditary spastic paraplegia (SPG43) previously described in two Malian sisters. Exome sequencing revealed a homozygous missense variant (c.187G>C; p.Ala63Pro) in C19orf12, a gene recently implicated in neurodegeneration with brain iron accumulation (NBIA). The same mutation was subsequently also found in a Brazilian family with features of NBIA, and we identified another NBIA patient with a three‐nucleotide deletion (c.197_199del; p.Gly66del). Haplotype analysis revealed that the p.Ala63Pro mutations have a common origin, but MRI scans showed no brain iron deposition in the Malian SPG43 subjects. Heterologous expression of these SPG43 and NBIA variants resulted in similar alterations in the subcellular distribution of C19orf12. The SPG43 and NBIA variants reported here as well as the most common C19orf12 missense mutation reported in NBIA patients are found within a highly conserved, extended hydrophobic domain in C19orf12, underscoring the functional importance of this domain. 相似文献
49.
50.
Hemostatic plug (HP) formation was investigated in the ear bleeding time incision in normal and von Willebrand pigs. HP volume was calculated by integrating the areas of serial sections. In normal pigs (n = 11), platelets immediately formed a layer on the surface of the cut channel. Platelet aggregates formed at the ends of transected vessels and gradually enlarged. Finally, all transected vessels were occluded by HP and bleeding stopped. In contrast, large HPs were formed in the incision in von Willebrand's disease (vWD) pigs (n = 4); these HPs did not cover the ends of the transected vessels, which continued to bleed, allowing the formation of large hemostatically ineffective platelet aggregates in the incision. Canals traversed these HPs, and bleeding from the open vessels may have continued through them. After infusion of cryoprecipitate into a vWD pig, the bleeding time shortened, and the morphological findings of the HPs were similar to those of normal pigs. In normal pigs (n = 3) infused with an anti- Willebrand factor monoclonal antibody, which prolonged the bleeding time, a large HP formed in the incision, similar to that observed in the vWD pig. The volume of the normal and vWD HPs increased with time. These in vivo findings suggest that Willebrand factor is involved in the localization of the HP to the damaged vessel and may also play a role in platelet-platelet interaction. A computerized morphometric technique was used for measuring the volume of the hemostatic plugs and the distance of sequential points on the perimeter of the HP from the center of selected bleeding vessels. 相似文献