全文获取类型
收费全文 | 775篇 |
免费 | 48篇 |
国内免费 | 3篇 |
专业分类
耳鼻咽喉 | 4篇 |
儿科学 | 44篇 |
妇产科学 | 8篇 |
基础医学 | 194篇 |
口腔科学 | 72篇 |
临床医学 | 84篇 |
内科学 | 111篇 |
皮肤病学 | 7篇 |
神经病学 | 53篇 |
特种医学 | 78篇 |
外科学 | 88篇 |
综合类 | 5篇 |
预防医学 | 31篇 |
眼科学 | 3篇 |
药学 | 19篇 |
肿瘤学 | 25篇 |
出版年
2023年 | 2篇 |
2022年 | 2篇 |
2021年 | 3篇 |
2020年 | 7篇 |
2019年 | 6篇 |
2018年 | 16篇 |
2017年 | 11篇 |
2016年 | 16篇 |
2015年 | 14篇 |
2014年 | 11篇 |
2013年 | 24篇 |
2012年 | 30篇 |
2011年 | 33篇 |
2010年 | 35篇 |
2009年 | 33篇 |
2008年 | 30篇 |
2007年 | 32篇 |
2006年 | 32篇 |
2005年 | 44篇 |
2004年 | 30篇 |
2003年 | 35篇 |
2002年 | 37篇 |
2001年 | 29篇 |
2000年 | 28篇 |
1999年 | 30篇 |
1998年 | 25篇 |
1997年 | 24篇 |
1996年 | 23篇 |
1995年 | 18篇 |
1994年 | 18篇 |
1993年 | 11篇 |
1992年 | 12篇 |
1991年 | 5篇 |
1990年 | 13篇 |
1989年 | 20篇 |
1988年 | 8篇 |
1987年 | 6篇 |
1986年 | 9篇 |
1985年 | 8篇 |
1984年 | 4篇 |
1983年 | 7篇 |
1982年 | 6篇 |
1981年 | 10篇 |
1980年 | 7篇 |
1979年 | 4篇 |
1978年 | 5篇 |
1977年 | 5篇 |
1976年 | 4篇 |
1975年 | 4篇 |
排序方式: 共有826条查询结果,搜索用时 15 毫秒
61.
Maria d’Apolito Daniela Pisanelli Flavio Faletra Ida Giardino Maddalena Gigante Massimo Pettoello-Mantovani Olivier Goulet Paolo Gasparini Angelo Campanozzi 《World journal of pediatrics : WJP》2016,12(2):219-224
Background
Congenital tufting enteropathy (CTE), an inherited autosomal recessive rare disease, is a severe diarrhea of infancy which is clinically characterized by absence of inflammation and presence of intestinal villous atrophy. Mutations in the EpCAM gene were identified to cause CTE. Recent cases of syndromic tufting enteropathy harboring the SPINT2 (19q13.2) mutation were described.Methods
Four CTE Italian patients were clinically and immunohistochemically characterized. Direct DNA sequencing of EpCAM and SPINT2 genes was performed.Results
All patients were of Italian origin. Three different mutations were detected (p.Asp219Metfs*15, Tyr186Phefs*6 and p.Ile146Asn) in the EpCAM gene; one of them is novel (p.Ile146Asn). Two patients (P1 and P2) showed compound heterozygosity revealing two mutations in separate alleles. A third patient (P3) was heterozygous for only one novel EpCAM missense mutation (p.Ile146Asn). In a syndromic patient (P4), no deleterious EpCAM mutation was found. Additional SPINT2 mutational analysis was performed. P4 showed a homozygous SPINT2 mutation (p.Y163C). No SPINT2 mutation was found in P3. CLDN7 was also evaluated as a candidate gene by mutational screening in P3 but no mutation was identified.Conclusion
This study presented a molecular characterization of CTE Italian patients, and identified three mutations in the EpCAM gene and one in the SPINT2 gene. One of EpCAM mutations was novel, therefore increasing the mutational spectrum of allelic variants of the EpCAM gene. Molecular analysis of the SPINT2 gene also allowed us to identify a SPINT2 substitution mutation (c.488A>G) recently found to be associated with syndromic CTE subjects.62.
63.
G Giavaresi M Fini P Torricelli L Martini R Giardino 《The International journal of artificial organs》2001,24(11):814-820
The effect of surgical ovariectomy on cancellous bone was investigated by comparing mechanical properties and microarchitectural characteristics of the lumbar vertebrae in ovariectomized and sham-operated ewes. Eighteen mongrel ewes, 4+/-1 years old, were randomly divided into three groups: 6 animals served as a control group (Baseline), 6 were bilaterally ovariectomized (OVX), and the others were used as a sham-operated group (SHAM). OVX and SHAM ewes were euthanized 24 months after surgery; the L5 vertebrae were processed for mechanical and histomorphometric analyses. Maximum load, maximum strength (p<0.0005) and elastic modulus (p <0.005) decreased by about 28% in the OVX group in comparison with the other groups. In the OVX group, vertebral cancellous bone volume, trabecular thickness and trabecular number decreased by about 32% (p<0.0005), 15% (p=0.001) and 20% (p=0.019), respectively. An overall decrease in the bone turnover rate of the OVX group was registered in terms of bone formation rate (p=0.007) and activation frequency (p<0.0005). The variations observed in cancellous bone mechanics and histomorphometry would suggest the development of an osteopenic state in ewe vertebrae at 24 months. Such findings may be useful for future experimental investigations on biomaterials and prosthetic devices to be implanted in the osteopenic spine. 相似文献
64.
The effect of lead chloride and cadmium chloride on in vitro immunoglobulin (Ig) production by human lymphocytes was investigated. After 7 days in culture, lead added in the range of human exposure (207-1035 micrograms/liter) significantly enhanced Ig production either when cells were activated by pokeweed mitogen (PWM) or not. The effect was dose-dependent and was related to the Pb we measured in the extracellular medium and in the cells. Independently of the mitogen addition, about 2% of the Pb added was accumulated in the cells, most being associated with the nuclear fraction. Those findings suggest that the Pb effects could depend on its uptake and distribution in the cells. Cadmium added in the 50-500 nM range exhibited a dose-independent mitogenic activity in unstimulated cells, whereas the Ig secretion was not significantly affected by Cd when cells were PWM-activated. A considerable intraindividual variability, however, was observed when blood donors were separately examined, with both an increase, a decrease, or no variation on Ig production. Furthermore, higher percentages of Cd were accumulated in the nuclear fraction, and lower in the cytosol and precipitate, in PWM-activated compared to resting lymphocytes. Genetic factors could be of importance for the observed variability of the immune response to cadmium, and we support the hypothesis that differences in the metallothionein (MT) inducibility could play a role. 相似文献
65.
Oral low-dose cyclophosphamide in metastatic hormone refractory prostate cancer (MHRPC). 总被引:3,自引:0,他引:3
A Nicolini Pa Mancini P Ferrari L Anselmi G Tartarelli V Bonazzi A Carpi R Giardino 《Biomedicine & Pharmacotherapy》2004,58(8):447-450
The chemotherapeutic approach to hormone-refractory metastatic prostate cancer (MHRPC) for a long time included only estramustine. Then, attempts have been made with other various agents as cyclophosphamide, vinblastine, etoposide, taxanes and carboplatinum. Although the new drugs and combinations have increased the response rate of MHRPC, they have had no impact on the natural history of MHRPC, which is about 1 year as median time of survival. After an occasional observation of prolonged response in a patient with MHRPC treated with a very well tolerated oral low-dose of cyclophosphamide, from February 1996 to October 2002, seven more patients with MHRPC and progressive disease were consecutively recruited. Response to treatment was evaluated by conventional radiological procedures and/or serial serum PSA measurements. The decline of PSA value was considered to assess the response consistent with the response guidelines from the prostate specific antigen-working group. All eight studied patients continuously received oral low dose cyclophosphamide until progression or the occurrence of significant toxicity. So far three patients (37.5%) progressed (PD), two (25%) showed PR and the three remaining SD. Response rate was 25%, and clinical benefit occurred in 62.5% of the studied patients. In the five patients with clinical benefit on cyclophosphamide median duration of clinical benefit, PR and SD were 9, 24+ and 8 months, respectively. In these five patients median overall survival times from cyclophosphamide and from the first regimen of chemotherapy were 17 and 33+ months respectively, while in the three patients with PD they were 4 and 13 months. The same interval times in patients with > or =50% decline of serum PSA were 29 and 50.5 months, while in those with <50% decline of the same marker, they were 13 and 32 months, respectively. Grade 2 or 3 neutropenia were observed in all the studied patients. In four (50%) of them pulmonary and urinary infections that were easily cured by the common antibiotics occurred. These data suggest that the metronomic use of cyclophosphamide, given alone, has similar or higher activity with lower toxicity than when administered with other active drugs. So it can be an useful option before or after the use of other single or combined potentially active chemotherapeutic agents. 相似文献
66.
Catastrophizing, or exaggerating the negative consequences of a situation, is associated with higher pain intensity, emotional distress, and functional disability among persons with chronic pain. According to the 'communal coping' model, catastrophizing in persons with pain may function as a social communication directed toward obtaining social proximity, support, or assistance. We tested the hypothesis, based on this model, that social factors would moderate the association between catastrophizing and sensory and affective pain. Seventy-four persons with a spinal cord injury and chronic pain completed measures of catastrophizing, solicitousness, depression, and sensory and affective pain before beginning a randomized controlled medication trial. Catastrophizing was significantly associated with solicitousness and pain reports. The association between catastrophizing and sensory pain scores was stronger for those who lived with a spouse or partner than for those who lived with someone else. In addition, there was a stronger association between catastrophizing and affective pain for those who reported greater solicitousness in their relationship. The results provide partial support for the communal coping model of catastrophizing. 相似文献
67.
Synaptopodin regulates the actin-bundling activity of alpha-actinin in an isoform-specific manner 下载免费PDF全文
Asanuma K Kim K Oh J Giardino L Chabanis S Faul C Reiser J Mundel P 《The Journal of clinical investigation》2005,115(5):1188-1198
Synaptopodin is the founding member of a novel class of proline-rich actin-associated proteins highly expressed in telencephalic dendrites and renal podocytes. Synaptopodin-deficient (synpo(-/-)) mice lack the dendritic spine apparatus and display impaired activity-dependent long-term synaptic plasticity. In contrast, the ultrastructure of podocytes in synpo(-/-) mice is normal. Here we show that synpo(-/-) mice display impaired recovery from protamine sulfate-induced podocyte foot process (FP) effacement and LPS-induced nephrotic syndrome. Similarly, synpo(-/-) podocytes show impaired actin filament reformation in vitro. We further demonstrate that synaptopodin exists in 3 isoforms, neuronal Synpo-short (685 AA), renal Synpo-long (903 AA), and Synpo-T (181 AA). The C terminus of Synpo-long is identical to that of Synpo-T. All 3 isoforms specifically interact with alpha-actinin and elongate alpha-actinin-induced actin filaments. synpo(-/-) mice lack Synpo-short and Synpo-long expression but show an upregulation of Synpo-T protein expression in podocytes, though not in the brain. Gene silencing of Synpo-T abrogates stress-fiber formation in synpo(-/-) podocytes, demonstrating that Synpo-T serves as a backup for Synpo-long in synpo(-/-) podocytes. In concert, synaptopodin regulates the actin-bundling activity of alpha-actinin in highly dynamic cell compartments, such as podocyte FPs and the dendritic spine apparatus. 相似文献
68.
Mixed lymphocyte reactivity and cell-mediated lympholysis to trinitrophenyl-modified autologous lymphocytes in C57BL/10 congenic and B10.A recombinant mouse strains 下载免费PDF全文
GM Shearer EC Lozner TG Rehn A Schmitt-Verhulst 《The Journal of experimental medicine》1975,141(4):930-934
Cell-mediated lympholysis (CML) to trinitrophenyl (TNP)-modified autologous splenic lymphocytes has been recently reported in the mouse (1). Both the sensitization and effector phases of this phenomenon were shown to be T-cell mediated. Effector cell specificity studies indicated that modification of the target cells is a necessary but insufficient requirement for cytolysis, and suggested that altered cell surface components controlled by genes mapping in the mouse major histocompatibility H-2 complex (MHC) are important in the specificity of the cytotoxic reaction (1). In allogeneic models the generation of cytotoxic effector cells has been shown to be preceded or accompanied by immunogen- induced proliferation of responding lymphocytes, i.e. a mixed lymphocyte reaction (MLR) (2-5), although the generation of effectors may not necessarily always be the consequence of extensive cell proliferation (5). If the induction of cytotoxic effector lymphocytes by modified syngeneic spleen cells is characteristic of sensitization with cellular alloantigens, one would expect to find that sensitization with TNP-modified autologous cells would also induce thymidine incorporation by the responding cells in the culture. The present report demonstrates that both stimulation of thymidine incorporation and generation of cytotoxic effector cells are part of the in vitro response to TNP-modified autologous lymphocytes. However, the MLR to TNP- modified autologous cells consistently appeared to be less pronounced when compared with an allogeneic MLR, whereas the cytotoxic activity of the effector cells generated by sensitization against TNP-modified autologous cells was frequently as high as that detected against H-2 alloantigens. These two components of reactivity to “modified self” are verified in several C57BL/10 congenic and B10.A recombinant mouse strains. 相似文献
69.
JB Gorlin ; EC Vamvakas ; E Cooke ; D Galacki ; R Geha ; D Humphreys ; P Kent 《Transfusion》1996,36(10):879-885
Background: Recruitment of progenitors during a large-volume collection, as defined by increasing relative and absolute numbers of progenitors (colony-forming units-granulocyte-macrophage [CFU-GM] of CD34+ cells), has been reported previously. Study Design and Methods: To ascertain whether intra-apheresis recruitment occurs in pediatric patients who have undergone mobilization with chemotherapy and granulocyte-colony-stimulating factor (G-CSF), each hour's portion of a 4-hour leukapheresis was collected into separate bags, and assessed by complete blood count, CFU-GM, and CD34+ cell assays. Seven pediatric patients (median age, 7; range, 2–19) were studied in connection with 2 to 4 collections each, for a total of 21 collections (with hourly samples). The collections lasted for 4 hours, at an inlet rate of 1 to 3 mL per kg per minute, for daily processing totals of 5 to 12 blood volumes. (One blood volume [mL] is estimated by the patient's weight in kg × 70 mL/kg.) Smaller (younger) patients had inlet rates exceeding 2 mL per kg per minute, and larger (older) patients had rates of 1 to 1.5 mL per kg per minute. CFU-GM and CD34+ cell counts obtained each hour of the collection and divided by the first hour's value were compared by nonparametric repeated-measures ANOVA. Results: Second-, third- and fourth-hour CD34+ progenitor cell counts were arithmetically higher than first-hour counts, but the trend did not reach significance (p = 0.1561). Second-hour counts were higher than first-hour counts in the overall analysis (mean ± standard error [SE], 1.00 and 1.39 ± 0.1, respectively; p = 0.0525) and in children older than 5 years (1.00 vs. 1.70 ± 0.30, respectively; p = 0.0259), but not in children younger than 5 years (p = 0.8125). CFU-GM counts did not differ among the 4 hours of collection (p = 0.1717) or between the first and second hour (p = 0.9587). Conclusion: In larger (older) patients, from whom fewer blood volumes were collected, there is a trend toward intra-apheresis recruitment, although less than reported previously. In the smaller (younger) patients, from whom more blood volumes were collected, no trend was observed. Lack of (or submaximal) prior mobilization in previously reported studies may have facilitated intracollection recruitment. Alternatively, the larger number of blood volumes collected from the smaller (younger) patients may have masked intra-apheresis recruitment. The study documents the feasibility of large-volume, 4-hour leukapheresis in pediatric patients. 相似文献
70.