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91.
Siobhan Flaherty Pamela Strauch Mahdi Maktabi Brandon S. Pybus Gregory Reichard Larry A Walker Rosemary Rochford 《Journal of cellular and molecular medicine》2022,26(13):3675
Primaquine (PQ) and Tafenoquine (TQ) are clinically important 8‐aminoquinolines (8‐AQ) used for radical cure treatment of P. vivax infection, known to target hepatic hypnozoites. 8‐AQs can trigger haemolytic anaemia in individuals with glucose‐6‐phosphate dehydrogenase deficiency (G6PDd), yet the mechanisms of haemolytic toxicity remain unknown. To address this issue, we used a humanized mouse model known to predict haemolytic toxicity responses in G6PDd human red blood cells (huRBCs). To evaluate the markers of eryptosis, huRBCs were isolated from mice 24–48 h post‐treatment and analysed for effects on phosphatidylserine (PS), intracellular reactive oxygen species (ROS) and autofluorescence. Urinalysis was performed to evaluate the occurrence of intravascular and extravascular haemolysis. Spleen and liver tissue harvested at 24 h and 5–7 days post‐treatment were stained for the presence of CD169+ macrophages, F4/80+ macrophages, Ter119+ mouse RBCs, glycophorin A+ huRBCs and murine reticulocytes (muRetics). G6PDd‐huRBCs from PQ/TQ treated mice showed increased markers for eryptosis as early as 24 h post‐treatment. This coincided with an early rise in levels of muRetics. Urinalysis revealed concurrent intravascular and extravascular haemolysis in response to PQ/TQ. Splenic CD169+ macrophages, present in all groups at day 1 post‐dosing were eliminated by days 5–7 in PQ/TQ treated mice only, while liver F4/80 macrophages and iron deposits increased. Collectively, our data suggest 8‐AQ treated G6PDd‐huRBCs have early physiological responses to treatment, including increased markers for eryptosis indicative of oxidative stress, resulting in extramedullary haematopoiesis and loss of splenic CD169+ macrophages, prompting the liver to act as the primary site of clearance. 相似文献
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93.
RueiLung Lin Hilaree N. Frazier Katie L. Anderson Sami L. Case Adam O. Ghoweri Olivier Thibault 《Aging cell》2022,21(7)
Neuronal hippocampal Ca2+ dysregulation is a critical component of cognitive decline in brain aging and Alzheimer''s disease and is suggested to impact communication and excitability through the activation of a larger after hyperpolarization. However, few studies have tested for the presence of Ca2+ dysregulation in vivo, how it manifests, and whether it impacts network function across hundreds of neurons. Here, we tested for neuronal Ca2+ network dysregulation in vivo in the primary somatosensory cortex (S1) of anesthetized young and aged male Fisher 344 rats using single‐cell resolution techniques. Because S1 is involved in sensory discrimination and proprioception, we tested for alterations in ambulatory performance in the aged animal and investigated two potential pathways underlying these central aging‐ and Ca2+‐dependent changes. Compared to young, aged animals displayed increased overall activity and connectivity of the network as well as decreased ambulatory speed. In aged animals, intranasal insulin (INI) increased network synchronicity and ambulatory speed. Importantly, in young animals, delivery of the L‐type voltage‐gated Ca2+ channel modifier Bay‐K 8644 altered network properties, replicating some of the changes seen in the older animal. These results suggest that hippocampal Ca2+ dysregulation may be generalizable to other areas, such as S1, and might engage modalities that are associated with locomotor stability and motivation to ambulate. Further, given the safety profile of INI in the clinic and the evidence presented here showing that this central dysregulation is sensitive to insulin, we suggest that these processes can be targeted to potentially increase motivation and coordination while also reducing fall frequency with age. 相似文献
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95.
J. Jansen M. Fedecostante M.J. Wilmer L.P. van den Heuvel J.G. Hoenderop R. Masereeuw 《Biotechnology advances》2014
With the world-wide increase of patients with renal failure, the development of functional renal replacement therapies have gained significant interest and novel technologies are rapidly evolving. Currently used renal replacement therapies insufficiently remove accumulating waste products, resulting in the uremic syndrome. A more preferred treatment option is kidney transplantation, but the shortage of donor organs and the increasing number of patients waiting for a transplant warrant the development of novel technologies. The bioartificial kidney (BAK) is such promising biotechnological approach to replace essential renal functions together with the active secretion of waste products. The development of the BAK requires a multidisciplinary approach and evolves at the intersection of regenerative medicine and renal replacement therapy. Here we provide a concise review embracing a compact historical overview of bioartificial kidney development and highlighting the current state-of-the-art, including implementation of living-membranes and the relevance of extracellular matrices. We focus further on the choice of relevant renal epithelial cell lines versus the use of stem cells and co-cultures that need to be implemented in a suitable device. Moreover, the future of the BAK in regenerative nephrology is discussed. 相似文献
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97.
Summary Two sugarbeet (Beta vulgaris L.) genotypes, REL-1 and REL-2, were used to measure the level of somatic embryo and shoot production from hormone-autonomous
callus plated under varied nutrient medium combinations of abscisic acid with the growth regulators 6-benzyladenine, 1-naphthaleneacetic
acid, or 2,4-dichlorophenoxyacetic acid, with eight sole nitrogen sources, or with different sucrose concentrations. Clone
REL-2 produced embryos up to 35-fold more frequently than clone REL-1. Inclusion of abscisic acid at some concentrations consistently
improved embryo production in all experiments and was observed to stimulate shoot production. At some concentrations, 1-naphthaleneacetic
acid as well as urea and glutamine stimulated greater embryo production over the control, but only for REL-1, for which there
was greater room for improvement. Three and five percent sucrose were superior to 1, 7, and 9%. Higher initial 6-benzyladenine
concentration [in the range 0, 0.1−1.0 mg/L (0.44−4.44 μM)] was associated with lower embryo production but greater shoot regeneration for both clones. REL-2 was significantly better
than REL-1 in shoot regeneration. The range of embryo production was more than 35-fold between genotypes, whereas the range
of physiological effects was no greater than 10-fold. REL-2 has been released to sugarbeet researchers because of its superior
embryogenic and shoot regeneration abilities for application in biotechnology. 相似文献
98.
Bardet–Biedl Syndrome is a multisystem autosomal recessive disorder characterized by central obesity, polydactyly, hypogonadism, learning difficulties, rod-cone dystrophy and renal dysplasia. Bardet–Biedl Syndrome has a prevalence rate ranging from 1 in 100,000 to 1 in 160,000 births although there are communities where Bardet–Biedl Syndrome is found at a higher frequency due to consanguinity. We report here a Pakistani consanguineous family with two affected sons with typical clinical features of Bardet–Biedl Syndrome, in addition to abnormal liver functioning and bilateral basal ganglia calcification, the latter feature being typical of Fahr's disease. Homozygous regions obtained from SNP array depicted three known genes BBS10, BBS14 and BBS2. Bidirectional sequencing of all coding exons by traditional sequencing of all these three genes showed a homozygous deletion of 10 nucleotides (c.1958_1967del), in BBS10 in both affected brothers. The segregation analysis revealed that the parents, paternal grandfather, maternal grandmother and an unaffected sister were heterozygous for the deletion. Such a large deletion in BBS10 has not been reported previously in any population and is likely to be contributing to the phenotype of Bardet–Biedl Syndrome in this family. 相似文献
99.
100.
本研究采用活性追踪的方法,逐步从人工培养蝉花虫草分离获得A(50%乙醇回流提取)、B(膜分离)、C(大孔树脂洗脱)和D(Sephadex LH20柱纯化)等4种样品,单一化合物D纯度为98.62%,鉴定为N6‐(2‐羟乙基)腺苷[N6‐(2‐hydroxyethyl)‐adenosine,HEA]。研究各样品对戊四唑(pentylenetetrazol,PTZ)诱导的小鼠惊厥模型的影响,以及选择性腺苷A1受体(AA1R)拮抗剂DPCPX或选择性腺苷A2A受体(AA2AR)拮抗剂ZM241385对HEA作用的影响,并采用苏木精-伊红(hematoxylin-eosin,HE)染色、免疫组化(immunohistochemical,IHC)染色和蛋白质免疫印迹(Western blot,WB)等技术进一步探究HEA抗惊厥作用的机制。结果表明,各样品(i.p.)均有抗惊厥活性,HEA(40–60mg/kg,i.p.)能显著延长惊厥小鼠的存活时间和降低死亡率,DPCPX(2mg/kg,i.p.)能够拮抗HEA的抗惊厥作用,而ZM241385无此作用;HE、IHC和WB的结果进一步揭示DPCPX显著降低HEA的作用。综上所述,蝉花虫草的HEA具有抗惊厥作用,并且可能通过激活腺苷A1受体而起作用。 相似文献