首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   3785篇
  免费   268篇
  2022年   14篇
  2021年   37篇
  2020年   36篇
  2019年   47篇
  2018年   65篇
  2017年   69篇
  2016年   107篇
  2015年   172篇
  2014年   174篇
  2013年   273篇
  2012年   302篇
  2011年   263篇
  2010年   200篇
  2009年   159篇
  2008年   241篇
  2007年   218篇
  2006年   206篇
  2005年   172篇
  2004年   182篇
  2003年   183篇
  2002年   166篇
  2001年   36篇
  2000年   41篇
  1999年   38篇
  1998年   47篇
  1997年   26篇
  1996年   27篇
  1995年   42篇
  1994年   37篇
  1993年   34篇
  1992年   25篇
  1991年   25篇
  1990年   36篇
  1989年   21篇
  1988年   17篇
  1987年   16篇
  1986年   11篇
  1985年   27篇
  1984年   34篇
  1983年   26篇
  1982年   19篇
  1981年   27篇
  1980年   10篇
  1979年   14篇
  1978年   14篇
  1977年   15篇
  1976年   10篇
  1975年   18篇
  1974年   8篇
  1971年   10篇
排序方式: 共有4053条查询结果,搜索用时 31 毫秒
1.
Detection of complex alleles by direct analysis of DNA heteroduplexes   总被引:3,自引:3,他引:0  
DNA molecules derived from three alleles of the HLA-DRB3 locus and differing from each other at several nucleotide sites were denatured and cross-hybridized. Each allelic combination was found to generate a pair of heteroduplexes of different mobility. Their retardation as compared to homoduplexes was proportional to the number of mismatches. In each heteroduplexes pair the component possessing the highest number of Pyr-Pyr oppositions was the most retarded. The results are those predicted by a theoretical model implying a correlation between base-pair opening and bending of the DNA double helix. These observations introduce a new HLA typing method at the genomic level and indicate an experimental approach to the analysis of the superhelical DNA conformation as related to different types of base oppositions.  相似文献   
2.
Upper airway muscles and the diaphragm may have different quantitative responses to chemoreceptor stimulation. To compare the respiratory muscle responses to changes in CO2, 10 ventilator-dependent preterm infants (gestational age 28 +/- 1 wk, postnatal age 40 +/- 6 days, weight 1.4 +/- 0.1 kg) were passively hyperventilated to apnea and subsequently hypoventilated. Electromyograms from the genioglossus, alae nasi, posterior cricoarytenoid, and diaphragm were recorded from surface electrodes. Apneic CO2 thresholds of all upper airway muscles (genioglossus 46.8 +/- 4.3 Torr, alae nasi 42.4 +/- 3.6 Torr, posterior cricoarytenoid 41.6 +/- 3.2 Torr) were higher than those of the diaphragm (38.8 +/- 2.6 Torr, all P less than 0.05). Above their CO2 threshold levels, responses of all upper airway muscles appeared proportional to those of the diaphragm. We conclude that nonproportional responses of the respiratory muscles to hypercapnia may be the result of differences in their CO2 threshold. These differences in CO2 threshold may cause imbalance in respiratory muscle activation with changes in chemical drive, leading to upper airway instability and obstructive apnea.  相似文献   
3.
Precise estimations of molecular rates are fundamental to our understanding of the processes of evolution. In principle, mutation and evolutionary rates for neutral regions of the same species are expected to be equal. However, a number of recent studies have shown that mutation rates estimated from pedigree material are much faster than evolutionary rates measured over longer time periods. To resolve this apparent contradiction, we have examined the hypervariable region (HVR I) of the mitochondrial genome using families of Adélie penguins (Pygoscelis adeliae) from the Antarctic. We sequenced 344 bps of the HVR I from penguins comprising 508 families with 915 chicks, together with both their parents. All of the 62 germline heteroplasmies that we detected in mothers were also detected in their offspring, consistent with maternal inheritance. These data give an estimated mutation rate (μ) of 0.55 mutations/site/Myrs (HPD 95% confidence interval of 0.29–0.88 mutations/site/Myrs) after accounting for the persistence of these heteroplasmies and the sensitivity of current detection methods. In comparison, the rate of evolution (k) of the same HVR I region, determined using DNA sequences from 162 known age sub-fossil bones spanning a 37,000-year period, was 0.86 substitutions/site/Myrs (HPD 95% confidence interval of 0.53 and 1.17). Importantly, the latter rate is not statistically different from our estimate of the mutation rate. These results are in contrast to the view that molecular rates are time dependent.  相似文献   
4.
5.

Introduction  

A proliferation-inducing ligand (APRIL) from the TNF family, owing to its role in the generation and survival of plasma cells (PCs), is currently targeted for rheumatoid arthritis (RA) treatment. However, little is known about APRIL expression in RA lesions, hampering our understanding of the way APRIL may modulate this autoimmune disease.  相似文献   
6.
Long-term depression (LTD) is a long-lasting activity-dependent decrease in synaptic strength. NMDA receptor (NMDAR)–dependent LTD, an extensively studied form of LTD, involves the endocytosis of AMPA receptors (AMPARs) via protein dephosphorylation, but the underlying mechanism has remained unclear. We show here that a regulated interaction of the endocytic adaptor RalBP1 with two synaptic proteins, the small GTPase RalA and the postsynaptic scaffolding protein PSD-95, controls NMDAR-dependent AMPAR endocytosis during LTD. NMDAR activation stimulates RalA, which binds and translocates widespread RalBP1 to synapses. In addition, NMDAR activation dephosphorylates RalBP1, promoting the interaction of RalBP1 with PSD-95. These two regulated interactions are required for NMDAR-dependent AMPAR endocytosis and LTD and are sufficient to induce AMPAR endocytosis in the absence of NMDAR activation. RalA in the basal state, however, maintains surface AMPARs. We propose that NMDAR activation brings RalBP1 close to PSD-95 to promote the interaction of RalBP1-associated endocytic proteins with PSD-95-associated AMPARs. This suggests that scaffolding proteins at specialized cellular junctions can switch their function from maintenance to endocytosis of interacting membrane proteins in a regulated manner.  相似文献   
7.

Background

Glatiramer acetate is worldwide used as first line treatment in relapsing remitting multiple sclerosis. Local skin reactions associated with glatiramer acetate are common, however, only isolated cases of severe local injection site reactions known as Nicolau Syndrome have been reported so far.

Case presentation

We describe the case of a recurrent Nicolau Syndrome occurred during longstanding glatiramer acetate treatment in a woman with multiple sclerosis. The haemorrhagic patch necrotized and was treated locally as a deep second degree burn with excision of dead skin tissue and was healed. Treatment with glatiramer acetate was definitely suspended.

Conclusions

GA injections can be complicated by isolated or recurrent Nicolau Syndrome, a potentially life-threatening condition of which neurologists should be aware.
  相似文献   
8.

Objective

In chronic kidney disease (CKD), both anemia and deregulated phosphate metabolism are common and predictive of adverse outcome. Previous studies suggest that iron status influences phosphate metabolism by modulating proteolytic cleavage of FGF23 into C-terminal fragments. Red cell distribution width (RDW) was recently identified as a strong prognostic determinant for cardiovascular morbidity and mortality, independently of iron status. We assessed whether RDW is associated with FGF23 cleaving in CKD patients with heart failure.

Materials and Methods

The associations between RDW and either intact FGF23 (iFGF23), C-terminal FGF23 (cFGF23, reflecting iFGF23 and C-terminal fragments together) and the iFGF23/cFGF23 ratio were analyzed in 52 patients with CKD (eGFR 34,9 ± 13.9 ml/min/1.73m2) and chronic heart failure (CHF). Associations between RDW and FGF23 forms were studied by linear regression analysis adjusted for parameters of renal function, iron metabolism, phosphate metabolism and inflammation.

Results

Median cFGF23 levels were 197.5 [110–408.5] RU/ml, median iFGF23 levels were 107.3 [65.1–162.2] pg/ml and median FGF23 ratio was 0.80 [0.37–0.86]. Mean RDW was 14.1 ± 1.2%. cFGF23 and RDW were associated (β = 1.63x10-3, P <0.001), whereas iFGF23 and RDW were not (β = -1.38x10-3, P = 0.336). The iFGF23/cFGF23 ratio was inversely associated with RDW. The difference between cFGF23 and iFGF23 (cFGF23- iFGF23) was positively associated with RDW (β = 1.74x10-3, P< 0.001). The association between cFGF23 and RDW persisted upon multivariable linear regression analysis, adjusted for parameters of renal function, phosphate metabolism, iron metabolism and inflammation (β = 0.97x10-3, P = 0.047).

Conclusion

RDW is associated with cFGF23 but not with iFGF23 levels in patients with CKD and CHF. This suggests a connection between RDW and FGF23 catabolism, independent of iron status and inflammation. Future studies are needed to unravel underlying mechanisms and whether these pertain to the link between RDW and outcome.  相似文献   
9.
Genetic diversity provides the raw material for populations to respond to changing environmental conditions. The evolution of diversity within populations is based on the accumulation of mutations and their retention or loss through selection and genetic drift, while migration can also introduce new variation. However, the extent to which population growth and sustained large population size can lead to rapid and significant increases in diversity has not been widely investigated. Here, we assess this empirically by applying approximate Bayesian computation to a novel ancient DNA dataset that spans the life of a southern elephant seal (Mirounga leonina) population, from initial founding approximately 7000 years ago to eventual extinction within the past millennium. We find that rapid population growth and sustained large population size can explain substantial increases in population genetic diversity over a period of several hundred generations, subsequently lost when the population went to extinction. Results suggest that the impact of diversity introduced through migration was relatively minor. We thus demonstrate, by examining genetic diversity across the life of a population, that environmental change could generate the raw material for adaptive evolution over a very short evolutionary time scale through rapid establishment of a large, stable population.  相似文献   
10.
In the last decades the growing awareness of the ecological importance of seagrass meadows has prompted increasing efforts to protect existing beds and restore degraded habitats. An in-depth knowledge of factors acting as major drivers of propagule settlement and recruitment is required in order to understand patterns of seagrass colonization and recovery and to inform appropriate management and conservation strategies. In this work Posidonia oceanica seedlings were reared for five months in a land-based culture facility under simulated natural hydrodynamic conditions to identify suitable substrates for seedling anchorage. Two main substrate features were investigated: firmness (i.e., sand vs. rock) and complexity (i.e., size of interstitial spaces between rocks). Seedlings were successfully grown in culture tanks, obtaining overall seedling survival of 93%. Anchorage was strongly influenced by substrate firmness and took place only on rocks, where it was as high as 89%. Anchorage occurred through adhesion by sticky root hairs. The minimum force required to dislodge plantlets attached to rocky substrates reached 23.830 N (equivalent to 2.43 kg), which would potentially allow many plantlets to overcome winter storms in the field. The ability of rocky substrates to retain seedlings increased with their complexity. The interstitial spaces between rocks provided appropriate microsites for seedling settlement, as seeds were successfully retained, and a suitable substrate for anchorage was available. In conclusion P. oceanica juveniles showed a clear-cut preference for hard substrates over the sandy one, due to the root system adhesive properties. In particular, firm and complex substrates allowed for propagule early and strong anchorage, enhancing persistence and establishment probabilities. Seedling substrate preference documented here leads to expect a more successful sexual recruitment on hard bottoms compared with soft ones. This feature could have influenced P. oceanica patterns of colonization in past and present time.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号