全文获取类型
收费全文 | 1643篇 |
免费 | 132篇 |
出版年
2023年 | 12篇 |
2022年 | 11篇 |
2021年 | 40篇 |
2020年 | 25篇 |
2019年 | 32篇 |
2018年 | 50篇 |
2017年 | 35篇 |
2016年 | 61篇 |
2015年 | 85篇 |
2014年 | 92篇 |
2013年 | 125篇 |
2012年 | 139篇 |
2011年 | 127篇 |
2010年 | 93篇 |
2009年 | 74篇 |
2008年 | 103篇 |
2007年 | 88篇 |
2006年 | 90篇 |
2005年 | 88篇 |
2004年 | 68篇 |
2003年 | 73篇 |
2002年 | 70篇 |
2001年 | 16篇 |
2000年 | 8篇 |
1999年 | 18篇 |
1998年 | 24篇 |
1997年 | 12篇 |
1996年 | 18篇 |
1995年 | 12篇 |
1994年 | 10篇 |
1993年 | 7篇 |
1992年 | 5篇 |
1991年 | 6篇 |
1990年 | 3篇 |
1989年 | 8篇 |
1988年 | 4篇 |
1987年 | 2篇 |
1986年 | 3篇 |
1985年 | 6篇 |
1984年 | 12篇 |
1983年 | 1篇 |
1982年 | 8篇 |
1981年 | 3篇 |
1980年 | 5篇 |
1979年 | 1篇 |
1976年 | 1篇 |
1956年 | 1篇 |
排序方式: 共有1775条查询结果,搜索用时 265 毫秒
151.
Robanus-Maandag E Bosch C Amini-Nik S Knijnenburg J Szuhai K Cervera P Poon R Eccles D Radice P Giovannini M Alman BA Tejpar S Devilee P Fodde R 《PloS one》2011,6(9):e24354
Desmoid tumours (also called deep or aggressive fibromatoses) are potentially life-threatening fibromatous lesions. Hereditary desmoid tumours arise in individuals affected by either familial adenomatous polyposis (FAP) or hereditary desmoid disease (HDD) carrying germline mutations in APC. Most sporadic desmoids carry somatic mutations in CTNNB1. Previous studies identified losses on 5q and 6q, and gains on 8q and 20q as recurrent genetic changes in desmoids. However, virtually all genetic changes were derived from sporadic tumours. To investigate the somatic alterations in FAP-associated desmoids and to compare them with changes occurring in sporadic tumours, we analysed 17 FAP-associated and 38 sporadic desmoids by array comparative genomic hybridisation and multiple ligation-dependent probe amplification. Overall, the desmoids displayed only a limited number of genetic changes, occurring in 44% of cases. Recurrent gains at 8q (7%) and 20q (5%) were almost exclusively found in sporadic tumours. Recurrent losses were observed for a 700 kb region at 5q22.2, comprising the APC gene (11%), a 2 Mb region at 6p21.2-p21.1 (15%), and a relatively large region at 6q15-q23.3 (20%). The FAP-associated desmoids displayed a significantly higher frequency of copy number abnormalities (59%) than the sporadic tumours (37%). As predicted by the APC germline mutations among these patients, a high percentage (29%) of FAP-associated desmoids showed loss of the APC region at 5q22.2, which was infrequently (3%) seen among sporadic tumours. Our data suggest that loss of region 6q15-q16.2 is an important event in FAP-associated as well as sporadic desmoids, most likely of relevance for desmoid tumour progression. 相似文献
152.
Pansini R 《PloS one》2011,6(7):e21993
Until now cooperation experiments in primates have paid little attention to how cooperation can emerge and what effects are produced on the structure of a social group in nature. I performed field experiments with three groups of wild vervet monkeys in South Africa. I induced individuals to repeatedly approach and operate food containers. At least two individuals needed to operate the containers in order to get the reward. The recurrent partner associations observed before the experiment only partly predicted the forming of cooperative partnerships during the experiment. While most of the tested subjects cooperated with other partners, they preferred to do so with specific combinations of individuals and they tended not to mix with other group members outside these preferred partnerships. Cooperation therefore caused the relatively homogeneous networks I observed before the experiment to differentiate. Similar to a matching market, the food sharing partners selected each other limiting their choice. Interestingly neither sex nor age classes explained the specific partner matching. Kinship could not explain it either. Rather, higher ranking individuals cooperated with other higher ranking individuals, and lower ranking also matched among the same rank. This study reveals the key role dominance rank plays when food resources are patchy and can only be accessed through sharing with other individuals. 相似文献
153.
Context
Levothyroxine monotherapy is the treatment of choice for hypothyroid patients because peripheral T4 to T3 conversion is believed to account for the overall tissue requirement for thyroid hormones. However, there are indirect evidences that this may not be the case in all patients.Objective
To evaluate in a large series of athyreotic patients whether levothyroxine monotherapy can normalize serum thyroid hormones and thyroid-pituitary feedback.Design
Retrospective study.Setting
Academic hospital.Patients
1,811 athyreotic patients with normal TSH levels under levothyroxine monotherapy and 3,875 euthyroid controls.Measurements
TSH, FT4 and FT3 concentrations by immunoassays.Results
FT4 levels were significantly higher and FT3 levels were significantly lower (p<0.001 in both cases) in levothyroxine-treated athyreotic patients than in matched euthyroid controls. Among the levothyroxine-treated patients 15.2% had lower serum FT3 and 7.2% had higher serum FT4 compared to euthyroid controls. A wide range of FT3/FT4 ratios indicated a major heterogeneity in the peripheral T3 production capacity in different individuals. The correlation between thyroid hormones and serum TSH levels indicated an abnormal feedback mechanism in levothyroxine-treated patients.Conclusions
Athyreotic patients have a highly heterogeneous T3 production capacity from orally administered levothyroxine. More than 20% of these patients, despite normal TSH levels, do not maintain FT3 or FT4 values in the reference range, reflecting the inadequacy of peripheral deiodination to compensate for the absent T3 secretion. The long-term effects of chronic tissue exposure to abnormal T3/T4 ratio are unknown but a sensitive marker of target organ response to thyroid hormones (serum TSH) suggests that this condition causes an abnormal pituitary response. A more physiological treatment than levothyroxine monotherapy may be required in some hypothyroid patients. 相似文献154.
Sperandeo MP Tosco A Izzo V Tucci F Troncone R Auricchio R Romanos J Trynka G Auricchio S Jabri B Greco L 《PloS one》2011,6(7):e21281
Background and Aim
Potential celiacs have the ‘celiac type’ HLA, positive anti-transglutaminase antibodies but no damage at small intestinal mucosa. Only a minority of them develops mucosal lesion. More than 40 genes were associated to Celiac Disease (CD) but we still do not know how those pathways transform a genetically predisposed individual into an affected person. The aim of the study is to explore the genetic features of Potential CD individuals.Methods
127 ‘potential’ CD patients entered the study because of positive anti-tissue transglutaminase and no mucosal lesions; about 30% of those followed for four years become frankly celiac. They were genotyped for 13 polymorphisms of ‘candidate genes’ and compared to controls and celiacs. Moreover, 60 biopsy specimens were used for expression studies.Results
Potential CD bear a lighter HLA-related risk, compared to celiac (χ2 = 48.42; p value = 1×10−8). They share most of the polymorphisms of the celiacs, but the frequency of c-REL* G allele was suggestive for a difference compared to celiac (χ2 = 5.42; p value = 0.02). One marker of the KIAA1109/IL-2/IL-21 candidate region differentiated potentials from celiac (rs4374642: χ2 = 7.17, p value = 0.01). The expression of IL-21 was completely suppressed in potentials compared to celiacs (p value = 0.02) and to controls (p value = 0.02), in contrast IL-2, KIAA1109 and c-REL expression were over-expressed.Conclusions
Potential CD show genetic features slightly different from celiacs. Genetic and expression markers help to differentiate this condition. Potential CD is a precious biological model of the pathways leading to the small intestinal mucosal damage in genetically predisposed individuals. 相似文献155.
The free sterol and phospholipid of the leaves and roots of Triticum aestivum var. MEC seedlings, grown at different temperatures, were determined. During growth, free sterols increased in the leaves and roots at optimum temperature (21°) whereas in the cold treatment (1°) they remained significantly unchanged despite an increase of cholesterol of the leaves indicating a higher degree of regulation of membrane structure under cold conditions. Phospholipid from both groups of plants increased in the leaves and in the roots during all the experimental period, although at a lower degree in the cold treated plants. The molar ratio of free sterol/phospholipids suggested a less ordered membrane structure in the cold treated leaves and roots. 相似文献
156.
Cobellis G Nicolaus G Iovino M Romito A Marra E Barbarisi M Sardiello M Di Giorgio FP Iovino N Zollo M Ballabio A Cortese R 《Nucleic acids research》2005,33(4):e44
In an effort to make transgenesis more flexible and reproducible, we developed a system based on novel 5′ and 3′ ‘gene trap’ vectors containing heterospecific Flp recognition target sites and the corresponding ‘exchange’ vectors allowing the insertion of any DNA sequence of interest into the trapped locus. Flp-recombinase-mediated cassette exchange was demonstrated to be highly efficient in our system, even in the absence of locus-specific selection. The feasibility of constructing a library of ES cell clones using our gene trap vectors was tested and a thousand insertion sites were characterized, following electroporation in ES cells, by RACE–PCR and sequencing. We validated the system in vivo for two trapped loci in transgenic mice and demonstrated that the reporter transgenes inserted into the trapped loci have an expression pattern identical to the endogenous genes. We believe that this system will facilitate in vivo studies of gene function and large-scale generation of mouse models of human diseases, caused by not only loss but also gain of function alleles. 相似文献
157.
158.
Neri M Filiberti R Taioli E Garte S Paracchini V Bolognesi C Canessa PA Fontana V Ivaldi GP Verna A Bonassi S Puntoni R 《Mutation research》2005,592(1-2):36-44
Pleural malignant mesothelioma (MM) is a rare but extremely aggressive cancer. The limited impact of standard therapeutic treatments on survival rates makes the identification of factors that increase the individual risk a leading priority. The high proportion of cases explained by exposure to asbestos has guided intervention policies to an effective ban of this compound from our environment. However, MM cannot be solely attributed to this agent, and the role of predisposing factors and their interaction with asbestos exposure is increasingly studied. The role of mEH, GSTM1, GSTT1, NAT2, and CYP1A1 genotypes in modulating susceptibility to MM was examined in a case-control study of 80 subjects with a confirmed diagnosis of MM and 255 controls. Subjects with low mEH activity showed a significantly increased risk of MM (OR, 2.51; 95% CI, 1.11-5.68). The association was stronger in the group with low asbestos exposure (OR, 7.83; 95% CI, 0.98-62.60). A significant increased risk of MM was also found in NAT2 fast acetylators (OR, 1.74; 95% CI, 1.02-2.96). The presence of synergisms between genotypes, i.e., mEH and NAT2 (LRT for heterogeneity p<0.023), mEH and GSTM1 (LRT p<0.061), and NAT2 and GSTM1 (LRT p<0.049), combined with the interaction observed with exposure to asbestos, suggests the presence of gene-environment and gene-gene interactions in the development of MM, although the size of the study group does not allow to draw clearcut conclusions. Since genetic polymorphisms can also modify the extent of genetic damage occurring in subjects exposed to carcinogens, we measured the frequency of micronuclei in peripheral blood lymphocytes of a subgroup of MM cases. The limited number of cases (28) did not allow to observe significant effects. In conclusion, these results strengthen the hypothesis that individual susceptibility to MM can be modulated by the interaction between polymorphic genes involved in the metabolism and the intensity of asbestos exposure. 相似文献
159.
Roberto Tognetti Riccardo d’Andria Giovanni Morelli Arturo Alvino 《Plant and Soil》2005,273(1-2):139-155
A field experiment on olive trees (Olea europaea L.) was designed with the objective to search for an optimum irrigation scheduling by analyzing the possible effects of deficit irrigation. Treatments were: a non-irrigated control (rainfed) and three treatments that received seasonal water amount equivalent to 33 and 66% of crop evapotranspiration (ETC) in the period August–September (respectively 33II and 66II), and 66% of (ETC) from late May to early October (66I-II). Atmospheric evaporative demand and soil moisture conditions were regularly monitored. Irrigation effects on plant water relations were characterized throughout a growing season. Whole-plant water use, in deficit irrigated (66I-II) and rainfed olive trees, was determined using a xylem sap flow method (compensation heat-pulse technique). The magnitude of variations in water use and the seasonal dynamic of water relations varied among treatments, suggesting that olive trees were strongly responsive to both irrigation amount and time. Physiological parameters responded to variations in tree water status, soil moisture conditions and atmospheric evaporative demand. All measurements of tree water status were highly correlated with one another. There was a considerable degree of agreement between daily transpiration deduced from heat-pulse velocity and that determined by calibration using the water balance technique. Deficit irrigation during the whole summer (66I-II) resulted in improved plant water relations with respect to other watering regimes; while, severe regulated deficit irrigation differentiated only slightly 33II treatment from rainfed plants. Nevertheless, regulated deficit irrigation of olive trees after pit hardening (66II) could be recommended, at least in soil, cultivar and environmental conditions of this study. 相似文献
160.
McGraw et al. (2004) have recently presented evidence that barnswallow (Hirundo rustica) feathers from the forehead and throatdo not 相似文献