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91.
92.
Körner A Kratzsch J Gausche R Blüher S Kapellen T Pulzer F Behrens M Kiess W 《Archives of physiology and biochemistry》2008,114(4):237-243
The clinical relevance of the term "metabolic syndrome", the definition criteria, and predictive power are being disputed. Inclusion of sleep-disordered breathing and sleep apnoea into a definition of metabolic syndrome is also controversial once children and/or adolescents are affected. Nevertheless, along with the increasing prevalence of childhood obesity, the prevalence of the metabolic syndrome in obese children is reported at 30%, irrespective of the definition applied. Moreover, childhood obesity is associated with sleep-disordered breathing. Adipocytokines, cytokines secreted from adipose tissue, are thought to play a major role in the pathophysiology of metabolic syndrome. Leptin was initially suggested as a promising "anti-obesity" hormone. New concepts indicate that in humans leptin and its soluble receptor may be more important in states of energy deficiency rather than a predictor of the metabolic syndrome. Adiponectin, on the other hand, is not only related to obesity and insulin resistance, but appears to be the strongest predictor for metabolic syndrome, even in children. In newborns and infants, both adipocytokines occur in high concentrations, even though this cannot completely explain the increased risk for ensuing metabolic disease later in life. Finally, low-grade systemic inflammation may underlie the clustering of metabolic risk factors. Overall factors from the adipose tissue may constitute not only markers but also mediators of metabolic sequelae of obesity. 相似文献
93.
Huebner AK Keller J Catala-Lehnen P Perkovic S Streichert T Emeson RB Amling M Schinke T 《Archives of biochemistry and biophysics》2008,473(2):210-217
The Calca gene encodes two polypeptides, calcitonin (CT) and α-calcitonin gene-related peptide (α-CGRP), generated through alternative splicing. While CT, a hormone mainly produced by thyroidal C cells, has been described as a major regulator of bone resorption, α-CGRP, a neuropeptide expressed in the cells of the central and peripheral nervous system, is mostly known as a regulator of vascular tone. Surprisingly, the generation and skeletal analyses of two mouse deficiency models has recently uncovered a physiological function for both peptides in the regulation of bone formation. In the first model, where the replacement of exons 2-5 of the Calca gene resulted in the combined deficiency of CT and α-CGRP, an increased bone formation rate (BFR) was observed, whereas decreased BFR was found in the second model, where the introduction of a translational termination codon into exon 5 of the Calca gene resulted in the specific absence of α-CGRP. 相似文献
94.
Penski N Härtle S Rubbenstroth D Krohmann C Ruggli N Schusser B Pfann M Reuter A Gohrbandt S Hundt J Veits J Breithaupt A Kochs G Stech J Summerfield A Vahlenkamp T Kaspers B Staeheli P 《Journal of virology》2011,85(15):7730-7741
From infection studies with cultured chicken cells and experimental mammalian hosts, it is well known that influenza viruses use the nonstructural protein 1 (NS1) to suppress the synthesis of interferon (IFN). However, our current knowledge regarding the in vivo role of virus-encoded NS1 in chickens is much more limited. Here, we report that highly pathogenic avian influenza viruses of subtypes H5N1 and H7N7 lacking fully functional NS1 genes were attenuated in 5-week-old chickens. Surprisingly, in diseased birds infected with NS1 mutants, the IFN levels were not higher than in diseased birds infected with wild-type virus, suggesting that NS1 cannot suppress IFN gene expression in at least one cell population of infected chickens that produces large amounts of the cytokine in vivo. To address the question of why influenza viruses are highly pathogenic in chickens although they strongly activate the innate immune system, we determined whether recombinant chicken alpha interferon (IFN-α) can inhibit the growth of highly pathogenic avian influenza viruses in cultured chicken cells and whether it can ameliorate virus-induced disease in 5-week-old birds. We found that IFN treatment failed to confer substantial protection against challenge with highly pathogenic viruses, although it was effective against viruses with low pathogenic potential. Taken together, our data demonstrate that preventing the synthesis of IFN is not the primary role of the viral NS1 protein during infection of chickens. Our results further suggest that virus-induced IFN does not contribute substantially to resistance of chickens against highly pathogenic influenza viruses. 相似文献
95.
With improvements in computer speed and algorithm efficiency, MD simulations are sampling larger amounts of molecular and biomolecular conformations. Being able to qualitatively and quantitatively sift these conformations into meaningful groups is a difficult and important task, especially when considering the structure-activity paradigm. Here we present a study that combines two popular techniques, principal component (PC) analysis and clustering, for revealing major conformational changes that occur in molecular dynamics (MD) simulations. Specifically, we explored how clustering different PC subspaces effects the resulting clusters versus clustering the complete trajectory data. As a case example, we used the trajectory data from an explicitly solvated simulation of a bacteria’s L11·23S ribosomal subdomain, which is a target of thiopeptide antibiotics. Clustering was performed, using K-means and average-linkage algorithms, on data involving the first two to the first five PC subspace dimensions. For the average-linkage algorithm we found that data-point membership, cluster shape, and cluster size depended on the selected PC subspace data. In contrast, K-means provided very consistent results regardless of the selected subspace. Since we present results on a single model system, generalization concerning the clustering of different PC subspaces of other molecular systems is currently premature. However, our hope is that this study illustrates a) the complexities in selecting the appropriate clustering algorithm, b) the complexities in interpreting and validating their results, and c) by combining PC analysis with subsequent clustering valuable dynamic and conformational information can be obtained. 相似文献
96.
Girke A Schierholt A Becker HC 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2012,124(6):1017-1026
Hybrid breeding relies on the combination of parents from two differing heterotic groups. However, the genetic diversity in
adapted oilseed rape breeding material is rather limited. Therefore, the use of resynthesized Brassica napus as a distant gene pool was investigated. Hybrids were derived from crosses between 44 resynthesized lines with a diverse
genetic background and two male sterile winter oilseed rape tester lines. The hybrids were evaluated together with their parents
and check cultivars in 2 years and five locations in Germany. Yield, plant height, seed oil, and protein content were monitored,
and genetic distances were estimated with molecular markers (127 polymorphic RFLP fragments). Resynthesized lines varied in
yield between 40.9 dt/ha and 21.5 dt/ha, or between 85.1 and 44.6% of check cultivar yields. Relative to check cultivars,
hybrids varied from 91.6 to 116.6% in yield and from 94.5 to 103.3% in seed oil content. Mid-parent heterosis varied from
−3.5 to 47.2% for yield. The genetic distance of parental lines was not significantly correlated with heterosis or hybrid
yield. Although resynthesized lines do not meet the elite rapeseed standards, they are a valuable source for hybrid breeding
due to their large distance from present breeding material and their high heterosis when combined with European winter oilseed
rape. 相似文献
97.
Brockschmidt A Filippi A Charbel Issa P Nelles M Urbach H Eter N Driever W Weber RG 《Human genetics》2011,130(5):645-655
In this study, we performed an in-depth analysis of the neurologic and ophthalmologic phenotype in a patient with Pitt–Hopkins
syndrome (PTHS), a disorder characterized by severe mental and motor retardation, carrying a uniallelic TCF4 deletion, and studied a zebrafish model. The PTHS-patient was characterized by high-resolution magnetic resonance imaging
(MRI) with diffusion tensor imaging to analyze the brain structurally, spectral-domain optical coherence tomography to visualize
the retinal layers, and electroretinography to evaluate retinal function. A zebrafish model was generated by knockdown of
tcf4-function by injection of morpholino antisense oligos into zebrafish embryos and the morphant phenotype was characterized
for expression of neural differentiation genes neurog1, ascl1b, pax6a, zic1, atoh1a, atoh2b. Data from PTHS-patient and zebrafish morphants were compared. While a cerebral MRI-scan showed markedly delayed myelination
and ventriculomegaly in the 1-year-old PTHS-patient, no structural cerebral anomalies including no white matter tract alterations
were detected at 9 years of age. Structural ocular examinations showed highly myopic eyes and an increase in ocular length,
while retinal layers were normal. Knockdown of tcf4-function in zebrafish embryos resulted in a developmental delay or defects in terminal differentiation of brain and eyes,
small eyes with a relative increase in ocular length and an enlargement of the hindbrain ventricle. In summary, tcf4-knockdown in zebrafish embryos does not seem to affect early neural patterning and regionalization of the forebrain, but
may be involved in later aspects of neurogenesis and differentiation. We provide evidence for a role of TCF4/E2-2 in ocular
growth control in PTHS-patients and the zebrafish model. 相似文献
98.
Zinger L Amaral-Zettler LA Fuhrman JA Horner-Devine MC Huse SM Welch DB Martiny JB Sogin M Boetius A Ramette A 《PloS one》2011,6(9):e24570
Background
Marine microbial communities have been essential contributors to global biomass, nutrient cycling, and biodiversity since the early history of Earth, but so far their community distribution patterns remain unknown in most marine ecosystems.Methodology/Principal Findings
The synthesis of 9.6 million bacterial V6-rRNA amplicons for 509 samples that span the global ocean''s surface to the deep-sea floor shows that pelagic and benthic communities greatly differ, at all taxonomic levels, and share <10% bacterial types defined at 3% sequence similarity level. Surface and deep water, coastal and open ocean, and anoxic and oxic ecosystems host distinct communities that reflect productivity, land influences and other environmental constraints such as oxygen availability. The high variability of bacterial community composition specific to vent and coastal ecosystems reflects the heterogeneity and dynamic nature of these habitats. Both pelagic and benthic bacterial community distributions correlate with surface water productivity, reflecting the coupling between both realms by particle export. Also, differences in physical mixing may play a fundamental role in the distribution patterns of marine bacteria, as benthic communities showed a higher dissimilarity with increasing distance than pelagic communities.Conclusions/Significance
This first synthesis of global bacterial distribution across different ecosystems of the World''s oceans shows remarkable horizontal and vertical large-scale patterns in bacterial communities. This opens interesting perspectives for the definition of biogeographical biomes for bacteria of ocean waters and the seabed. 相似文献99.
Birkenfeld AL Lee HY Guebre-Egziabher F Alves TC Jurczak MJ Jornayvaz FR Zhang D Hsiao JJ Martin-Montalvo A Fischer-Rosinsky A Spranger J Pfeiffer AF Jordan J Fromm MF König J Lieske S Carmean CM Frederick DW Weismann D Knauf F Irusta PM De Cabo R Helfand SL Samuel VT Shulman GI 《Cell metabolism》2011,14(2):184-195
Reduced expression of the Indy (I'm Not Dead, Yet) gene in D.?melanogaster and its homolog in C.?elegans prolongs life span and in D.?melanogaster augments mitochondrial biogenesis in a manner akin to caloric restriction. However, the cellular mechanism by which Indy does this is unknown. Here, we report on the knockout mouse model of the mammalian Indy (mIndy) homolog, SLC13A5. Deletion of mIndy in mice (mINDY(-/-) mice) reduces hepatocellular ATP/ADP ratio, activates hepatic AMPK, induces PGC-1α, inhibits ACC-2, and reduces SREBP-1c levels. This signaling network promotes hepatic mitochondrial biogenesis, lipid oxidation, and energy expenditure and attenuates hepatic de novo lipogenesis. Together, these traits protect mINDY(-/-) mice from the adiposity and insulin resistance that evolve with high-fat feeding and aging. Our studies demonstrate a profound effect of mIndy on mammalian energy metabolism and suggest that mINDY might be a therapeutic target for the treatment of obesity and type 2 diabetes. 相似文献
100.