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991.
Approaching the degradome in idiopathic pulmonary fibrosis 总被引:1,自引:0,他引:1
Pardo A Selman M Kaminski N 《The international journal of biochemistry & cell biology》2008,40(6-7):1141-1155
Idiopathic pulmonary fibrosis (IPF) is a devastating, lethal and currently untreatable lung disorder of unknown etiology. It is characterized by epithelial injury and activation, fibroblastic foci formation, and exaggerated accumulation of extracellular matrix (ECM) with the destruction of the lung parenchyma. Despite important progress in our understanding of the general mechanisms involved in lung fibrogenesis, the pathogenesis of the IPF remains unclear. Although the irreversible and progressive fibrosis in the lung suggests a decrease in lung degradative machinery, an increasing body of evidence, primarily obtained by global gene expression studies, demonstrates a significant upregulation of degrading enzymes in IPF. In this context, this review will focus on some families of the degradome, a term proposed for the complete set of proteases that are expressed at a specific time by a cell, tissue or an organism. In particular, we will approach recent progress in our understanding of the behavior of two families of metalloproteases M10 and M12 which are significantly changed in the IPF lungs. In general, evidence highlights the increasing diversity in both substrates and functions of these enzymes and the complexity of the processes in which they are involved, and indicate a critical role in the abnormal remodeling of IPF. 相似文献
992.
993.
994.
Annie Britton Martin Shipley Michael Marmot Harry Hemingway 《BMJ (Clinical research ed.)》2004,329(7461):318
Objective To determine whether access to cardiac procedures and drugs contributes to social and ethnic differences in coronary heart disease in a population setting.Design Prospective study with follow up over 15 years. Civil service employment grade was used as a measure of individual socioeconomic position. Need for cardiac care was determined by the presence of angina, myocardial infarction, and coronary risk factors.Setting 20 civil service departments originally located in London.Participants 10 308 civil servants (3414 women; 560 South Asian) aged 35-55 years at baseline in 1985-8.Main outcome measures Use of exercise electrocardiography, coronary angiography, and coronary revascularisation procedures and secondary prevention drugs.Results Inverse social gradients existed in incident coronary morbidity and mortality. South Asian participants also had higher rates than white participants. After adjustment for clinical need, social position showed no association with the use of cardiac procedures or secondary prevention drugs. For example, men in the low versus high employment grade had an age adjusted odds ratio for angiography of 1.87 (95% confidence interval 1.32 to 2.64), which decreased to 1.27 (0.83 to 1.94) on adjustment for clinical need. South Asians tended to be more likely to have cardiac procedures and to be taking more secondary prevention drugs than white participants, even after adjustment for clinical need.Conclusion This population based study, which shows the widely observed social and ethnic patterning of coronary heart disease, found no evidence that low social position or South Asian ethnicity was associated with lower use of cardiac procedures or drugs, independently of clinical need. Differences in medical care are unlikely to contribute to social or ethnic differences in coronary heart disease in this cohort. 相似文献
995.
The use and advantage of flow cytometry as a particle-by-particle, low sampling volume, high-throughput screening technique for quantitatively examining the non-specific adsorption of proteins onto surfaces is presented. The adsorption of three proteins: bovine serum albumin (BSA), immunoglobulin gamma (IgG) and protein G, incubated at room temperature for 2 h onto organosilica particles modified with poly(ethylene glycol) (PEG) of increasing MW (2000, 3400, 6000, 10,000 and 20,000 g mol(-1)) and grafted amounts (0.14-1.4 mg m(-2)) was investigated as a model system. Each protein exhibited Langmuir-like, high affinity monolayer limited adsorption on unmodified particles with the proteins reaching surface saturation at 1.8, 4.0 and 2.5 mg m(-2) for BSA, IgG and protein G, respectively. Protein adsorption on PEG-modified surfaces was found to decrease with increasing amounts of grafted polymer. PEG grafting amounts >0.6 mg m(-2) effectively prevented the adsorption of the larger two proteins (BSA and IgG) while a PEG grafting amount >1.3 mg m(-2) was required to prevent the adsorption of the smaller protein G. 相似文献
996.
Quantitative trait locus analysis for hemostasis and thrombosis 总被引:1,自引:0,他引:1
Qila Sa Erika Hart Annie E. Hill Joseph H. Nadeau Jane L. Hoover-Plow 《Mammalian genome》2008,19(6):406-412
Susceptibility to thrombosis varies in human populations as well as many in inbred mouse strains. The objective of this study
was to characterize the genetic control of thrombotic risk on three chromosomes. Previously, utilizing a tail-bleeding/rebleeding
assay as a surrogate of hemostasis and thrombosis function, three mouse chromosome substitution strains (CSS) (B6-Chr5A/J, Chr11A/J
, Chr17A/J) were identified (Hmtb1, Hmtb2, Hmtb3). The tail-bleeding/rebleeding assay is widely used and distinguishes mice with genetic defects in blood clot formation or
dissolution. In the present study, quantitative trait locus (QTL) analysis revealed a significant locus for rebleeding (clot
stability) time (time between cessation of initial bleeding and start of the second bleeding) on chromosome 5, suggestive
loci for bleeding time (time between start of bleeding and cessation of bleeding) also on chromosomes 5, and two suggestive
loci for clot stability on chromosome 17 and one on chromosome 11. The three CSS and the parent A/J had elevated clot stability
time. There was no interaction of genes on chromosome 11 with genes on chromosome 5 or chromosome 17. On chromosome 17, twenty-three
candidate genes were identified in synteny with previously identified loci for thrombotic risk on human chromosome 18. Thus,
we have identified new QTLs and candidate genes not previously known to influence thrombotic risk.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
997.
Few genetic data document the postglacial history of the western house mouse, Mus musculus domesticus. We address this by studying a sample from the southeastern tip of the Fertile Crescent in the Iranian province of Ahvaz. Including other published and unpublished data from France, Germany, Italy, Bulgaria, Turkey and other places in Iran, altogether 321 mitochondrial D-loop sequences are simultaneously analysed. The patterns of coalescence obtained corroborate the classical proposal according to which the Fertile Crescent is where commensalism with humans has started in the Western Hemisphere, and from where the subspecies has expanded further west. Our data also clearly show that despite multiple colonisations and long-range transportation, there is still a rather high PhiST of 0.39. The original expansion signal is still recognisable, with two well-separated derived clades, allowing us to propose a hypothetical scenario in which expansion toward Europe and Asia Minor took at least two routes, tentatively termed the Mediterranean and the Bosphorus/Black Sea routes. This scenario resembles that of another domesticated species, the goat, and fits with the known progression of Neolithic culture. Given the concomitance of both phenomena around 12,000 years ago, we propose a recalibration of the D-loop mutation rate to a much faster tick of approximately 40% per site per million years (Myr). This value should be used for intrasubspecific polymorphism, while the interspecific rate in Mus is presently estimated at 6-10%/site/Myr. This is in keeping with the now well recognised fact that only a subfraction of segregating mutations go to fixation. 相似文献
998.
Age-dependent xylogenesis in timberline conifers 总被引:3,自引:0,他引:3
Neither anatomical change nor physiological abnormalities have been observed in the cambia of older trees. However, different sensitivity and period of significant responses to climate suggest the existence of some age-related change in the patterns of cambial activity and/or wood cell formation. Here, weekly cambial activity and timing and duration of xylem cell enlargement and wall thickening were compared in adult (50-80 yr) and old (200-350 yr) trees of Larix decidua, Pinus cembra and Picea abies at the Alpine timberline during 2004 and 2005. Timings and durations of xylogenesis differed between adult and old trees, with 2-3 wk shorter cambial activity found in the latter. The delayed onset of cambium division and lower cell production in old trees, with respect to adult trees, led to reductions of 15-20% in the overall duration of xylem differentiation. These results demonstrate that cambial dynamics change during the tree lifespan and that the time window of tree-ring production shortens with age. Variations in the period of xylem growth may be the cause of age-dependent responses to climate. The observed shorter xylogenesis in older plants at the Alpine timberline could be related to a size effect and not just to age per se. 相似文献
999.
Gerard Leblondel Yves Mauras Annie Cailleux Pierre Allain 《Biological trace element research》2001,83(3):191-206
The transport and uptake of the most common Se compounds, selenate (SeO
4
2−
), selenite (SeO
3
2−
), selenomethionine, and selenocystine, were investigated using confluent monolayers of Caco-2 cells, a human carcinoma cell
line. Comparative measurements were performed in the absorptive (apical to basolateral side) and exsorptive (basolateral to
apical side) directions. Apparent permeability coefficients (P
app), calculated from transport experiments in the absorptive direction, showed increasing values in the following rank order:
about 1×10−6 cm/s ≤ mannitol ≤ SeO
3
2−
≤ selenocystine < selenomethionine < SeO
4
2−
≤ about 16×10−6 cm/s. The ratios of the P
app measured in the absorptive versus exsorptive directions indicated that only the organic forms presented a net polarized transport
(P
app ratio ≫1), suggesting the presence of a transcellular pathway. No significant excretion was observed. The transport of selenomethionine
was inhibited by its sulfur analog, methionine, suggesting a common transport mechanism. In contrast, an inhibition of the
transport of selenocystine by cysteine was not observed. From the two substrates tested, sulfate and thiosulfate, only thiosulfate
inhibited the transport of SeO
4
2−
. This effect was also observed for SeO
3
2−
(i.e., was unspecific), which questioned the assertion of a common transport for sulfate and SeO
4
2−
and may confirm the paracellular pathway of SeO
4
2−
suggested by the P
app ratio of about 1. The addition of glutathione (GSH) in large excess had no consequence on the passage of SeO
3
2−
but strongly increased the uptake (about fourfold). The liquid chromatography — mass spectrometry (LC-MS) data showed that,
in the ionic condition of incubation medium, GSH promptly reduced SeO
3
2−
(≤2 min) in its elemental form Se0, which cannot ascribe to selenodiglutathione a direct role in the effect of GSH. 相似文献
1000.
Effects of habitat transition on the evolutionary patterns of the microgastropod genus Pseudamnicola (Mollusca,Hydrobiidae) 下载免费PDF全文
Molecular phylogenies of extant species are considered effective tools to infer mechanisms of speciation. Here, we benefit from this utility to investigate the evolutionary history of an organismal group linked to different aquatic ecosystems, the microgastropod genus Pseudamnicola (family Hydrobiidae). Previous studies have found around 45 species of the nominal subgenus P. (Pseudamnicola), most of them in coastal stream localities of several Mediterranean islands and mainland territories, whereas only 12 species of the other subgenus, P. (Corrosella), have been collected from springs and headwaters of mountainous regions of the Iberian Peninsula and south of France. As springs often act as isolated habitats affecting dispersion and constraining gene flow, we supposed that the temporal history and mode of diversification of species from both subgenera should differ and therefore be reflected in their phylogenetic patterns. To assess this hypothesis, we performed a molecular phylogeny based on mitochondrial and nuclear DNA sequences and later conducted an independent analysis to examine the potential effect of certain geographic and ecological variables in the genetic divergences of the subgenera. Additionally, we estimated the ancestral area of diversification of both groups. Published anatomical revisions and our molecular analyses suggest that the genus Pseudamnicola should be divided into three genera: the two previous subgenera plus a new one described here. As postulated, the evolution of the spring organisms was strongly related to habitat fragmentation and isolation, whereas dispersal followed by divergence seem to have been the most common speciation processes for euryhaline species inhabiting coastal streams and low river stages in which waters remain connected. On the contrary, rather than habitat fragmentation or dispersion, environmental conditions have played a larger role during the deep divergent split leading to the three genera. 相似文献