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941.
Jean-Marie Normand Maria V. Sanchez-Vives Christian Waechter Elias Giannopoulos Bernhard Grosswindhager Bernhard Spanlang Christoph Guger Gudrun Klinker Mandayam A. Srinivasan Mel Slater 《PloS one》2012,7(10)
Immersive virtual reality (IVR) typically generates the illusion in participants that they are in the displayed virtual scene where they can experience and interact in events as if they were really happening. Teleoperator (TO) systems place people at a remote physical destination embodied as a robotic device, and where typically participants have the sensation of being at the destination, with the ability to interact with entities there. In this paper, we show how to combine IVR and TO to allow a new class of application. The participant in the IVR is represented in the destination by a physical robot (TO) and simultaneously the remote place and entities within it are represented to the participant in the IVR. Hence, the IVR participant has a normal virtual reality experience, but where his or her actions and behaviour control the remote robot and can therefore have physical consequences. Here, we show how such a system can be deployed to allow a human and a rat to operate together, but the human interacting with the rat on a human scale, and the rat interacting with the human on the rat scale. The human is represented in a rat arena by a small robot that is slaved to the human’s movements, whereas the tracked rat is represented to the human in the virtual reality by a humanoid avatar. We describe the system and also a study that was designed to test whether humans can successfully play a game with the rat. The results show that the system functioned well and that the humans were able to interact with the rat to fulfil the tasks of the game. This system opens up the possibility of new applications in the life sciences involving participant observation of and interaction with animals but at human scale. 相似文献
942.
Andrius Serva Bettina Knapp Yueh-Tso Tsai Christoph Claas Tautvydas Lisauskas Petr Matula Nathalie Harder Lars Kaderali Karl Rohr Holger Erfle Roland Eils Vania Braga Vytaute Starkuviene 《PloS one》2012,7(12)
miRNA cluster miR-17-92 is known as oncomir-1 due to its potent oncogenic function. miR-17-92 is a polycistronic cluster that encodes 6 miRNAs, and can both facilitate and inhibit cell proliferation. Known targets of miRNAs encoded by this cluster are largely regulators of cell cycle progression and apoptosis. Here, we show that miRNAs encoded by this cluster and sharing the seed sequence of miR-17 exert their influence on one of the most essential cellular processes – endocytic trafficking. By mRNA expression analysis we identified that regulation of endocytic trafficking by miR-17 can potentially be achieved by targeting of a number of trafficking regulators. We have thoroughly validated TBC1D2/Armus, a GAP of Rab7 GTPase, as a novel target of miR-17. Our study reveals regulation of endocytic trafficking as a novel function of miR-17, which might act cooperatively with other functions of miR-17 and related miRNAs in health and disease. 相似文献
943.
Luigi Laghi Stefania Beghelli Antonino Spinelli Paolo Bianchi Gianluca Basso Giuseppe Di Caro Anna Brecht Giuseppe Celesti Giona Turri Samantha Bersani Guido Schumacher Christoph R?cken Ilona Gr?ntzd?rffer Massimo Roncalli Alessandro Zerbi Peter Neuhaus Claudio Bassi Marco Montorsi Aldo Scarpa Alberto Malesci 《PloS one》2012,7(9)
Background and Aims
Pancreatic cancer risk is increased in Lynch syndrome (LS) patients with mismatch repair gene defects predisposing to colonic and extracolonic cancers with microsatellite instability (MSI). However, the frequency of MSI pancreatic cancers has never been ascertained in consecutive, unselected clinical series, and their contribution to the sporadic and inherited burden of pancreatic cancer remains to be established. Aims of the study were to determine the prevalence of MSI in surgically resected pancreatic cancers in a multicentric, retrospective study, and to assess the occurrence of pancreatic cancer in LS.Methods
MS-status was screened by a panel of 5 mononucleotide repeats (Bat26, Bat25, NR-21, NR-24 and NR-27) in 338 consecutive pancreatic ductal adenocarcinoma (PDAC), resected at two Italian and one German referral centres. The personal history of pancreatic cancer was assessed in an independent set of 58 probands with LS and in 138 first degree relatives who had cancers.Results
Only one PDAC (0.3%) showed MSI. This was a medullary type cancer, with hMLH1-deficiency, and no identified germ-line mutation but methylation of hMLH1. Pancreatic cancer occurred in 5 (2.5%) LS patients. Histological sampling was available for 2 cases, revealing PDAC in one case and an ampullary cancer in the other one.Conclusions
MSI prevalence is negligible in sporadic, resected PDAC. Differently, the prevalence of pancreatic cancer is 2.5% in LS patients, and cancers other than PDAC may be encountered in this setting. Surveillance for pancreatic cancer should be advised in LS mutation carriers at referral centers. 相似文献944.
Glycodelin protein and mRNA is downregulated in human first trimester abortion and partially upregulated in mole pregnancy. 总被引:1,自引:0,他引:1
Bettina Toth Karin Roth Christiane Kunert-Keil Christoph Scholz Sandra Schulze Ioannis Mylonas Klaus Friese Udo Jeschke 《The journal of histochemistry and cytochemistry》2008,56(5):477-485
Glycodelin (Gd) is a major reproductive glycoprotein and a mediator for immunomodulatory effects directed to cellular, humoral, and innate immunity. Human pregnancy depends on a diversity of physiological processes including modulation of the maternal immunosystem. We evaluated the expression of Gd protein and mRNA in first trimester decidual tissue of normal pregnancies and spontaneous abortion and hydatidiform moles. Furthermore, in vitro experiments on endometrial cancer cells to analyze the effect of human chorionic gonadotropin (hCG) on Gd regulation were performed. In decidual tissue of abortion patients, Gd expression was significantly decreased compared with normal gestation, which was confirmed by in situ hybridization. In mole pregnancy, an upregulation of Gd in the first 8 weeks of pregnancy was present. Gd is a main product of decidual tissue in the first trimester of human pregnancy. Reduced Gd expression in abortive pregnancy could lead to an increased activation of the maternal immunosystem, thus causing rejection of the developing fetus. Moreover, Gd expression in endometrial cancer cells in vitro could be stimulated by addition of hCG. Therefore, we speculate that hCG could be one of the factors regulating Gd expression because hCG is downregulated in women with abortion and upregulated in mole pregnancy. In addition, we found a positive feedback loop in Gd and hCG expression in human pregnancy. 相似文献
945.
Kuhlmann CR Gerigk M Bender B Closhen D Lessmann V Luhmann HJ 《Life sciences》2008,82(25-26):1281-1287
Glutamate is an important excitatory amino acid in the central nervous system. Under pathological conditions glutamate levels dramatically increase. Aim of the present study was to examine whether the HMG-CoA inhibitor fluvastatin prevents glutamate-induced blood-brain-barrier (BBB) disruption. Measurements of transendothelial electrical resistance (TEER) were performed to analyze BBB integrity in an in vitro co-culture model of brain endothelial and glial cells. Myosin light chain (MLC) phosphorylation was detected by immunohistochemistry, or using the in-cell western technique. Intracellular Ca2+ and reactive oxygen species (ROS) levels were analyzed using the fluorescence dyes Ca-green or DCF. Glutamate induced a time- (1-3 h) and concentration- (0.25-1 mmol/l) dependent decrease of TEER values that was blocked by the NMDA-receptor antagonist MK801, the Ca2+ chelator BAPTA, the NAD(P)H-oxidase inhibitor apocynin and the MLC-kinase inhibitor ML-7. Furthermore we observed a concentration-dependent increase of intracellular Ca2+ and ROS after glutamate application. Glutamate caused an increase of MLC phosphorylation that was antagonized by apocynin, or BAPTA, indicating that Ca2+ and ROS signaling is involved in the activation of the contractile machinery. Fluvastatin (10-25 micromol/l) completely abolished the glutamate-induced barrier disruption and oxidative stress. The BBB-protecting effect of fluvastatin was completely lost if the cells were treated with the nitric oxide (NO) synthase inhibitor L-NMMA (300 micromol/l). In the present study we demonstrated that glutamate-induced BBB disruption involves Ca2+ signalling via NMDA receptors, which is followed by an increased ROS generation by the NAD(P)H-oxidase. This oxidative stress then activates the MLC kinase. Fluvastatin preserves barrier function in a NO-dependent way and reduces glutamate-induced oxidative stress. 相似文献
946.
Christoph Randler 《Journal of Ethology》2008,26(3):309-316
Predation is one of the most selective forces in evolution and, thus, predation may select against hybrids in narrow hybrid
zones. It may be possible that parental phenotypes and hybrids differ in their responses towards predators or humans. As predation
is difficult to observe I used flight-initiation distance (FID) as a metric of risk assessment. FID is a measurable outcome
of the trade-off between fleeing and remaining. Here, I tested whether hybrid and parent crow phenotypes (Corvus corone, Corvus cornix) from the hybrid zone in Eastern Germany differ in their FID. Further, I measured many environmental and social variables
to control statistically for their influence on FID. I sampled 154 individuals (53 hooded crows, 54 carrion crows, and 48
hybrids) in the hybrid zone in eastern Germany. I calculated a general linear model using a stepwise backward procedure to
establish a minimum model containing only significant variables that explained FID in crows. The variable phenotype (hooded,
carrion, hybrid) was then added to the model. There were no differences in FID between hybrids and both parental phenotypes
types, suggesting similar risk assessment. This suggests that hybrids may behave similarly in their decision to flee as their
parent phenotypes, which, in turn, provides no evidence for a selective disadvantage. An additional analysis focusing on pure
phenotypic flocks showed that hybrids in pure hybrid flocks had a lower FID than both parental species in pure flocks. This
suggests that hybrids in pure hybrid flocks may be at a disadvantage. 相似文献
947.
948.
Structural basis for LEAFY floral switch function and similarity with helix-turn-helix proteins 总被引:1,自引:0,他引:1
Hamès C Ptchelkine D Grimm C Thevenon E Moyroud E Gérard F Martiel JL Benlloch R Parcy F Müller CW 《The EMBO journal》2008,27(19):2628-2637
The LEAFY (LFY) protein is a key regulator of flower development in angiosperms. Its gradually increased expression governs the sharp floral transition, and LFY subsequently controls the patterning of flower meristems by inducing the expression of floral homeotic genes. Despite a wealth of genetic data, how LFY functions at the molecular level is poorly understood. Here, we report crystal structures for the DNA-binding domain of Arabidopsis thaliana LFY bound to two target promoter elements. LFY adopts a novel seven-helix fold that binds DNA as a cooperative dimer, forming base-specific contacts in both the major and minor grooves. Cooperativity is mediated by two basic residues and plausibly accounts for LFY's effectiveness in triggering sharp developmental transitions. Our structure reveals an unexpected similarity between LFY and helix-turn-helix proteins, including homeodomain proteins known to regulate morphogenesis in higher eukaryotes. The appearance of flowering plants has been linked to the molecular evolution of LFY. Our study provides a unique framework to elucidate the molecular mechanisms underlying floral development and the evolutionary history of flowering plants. 相似文献
949.
950.
According to a long-standing hypothesis, aging is mainly caused by accumulation of nuclear (n) DNA damage in differentiated cells such as neurons due to insufficient nDNA repair during lifetime. In line with this hypothesis it was until recently widely accepted that neuron loss is a general consequence of normal aging, explaining some degree of decline in brain function during aging. However, with the advent of more accurate procedures for counting neurons, it is currently widely accepted that there is widespread preservation of neuron numbers in the aging brain, and the changes that do occur are relatively specific to certain brain regions and types of neurons. Whether accumulation of nDNA damage and decline in nDNA repair is a general phenomenon in the aging brain or also shows cell-type specificity is, however, not known. It has not been possible to address this issue with the biochemical and molecular-biological methods available to study nDNA damage and nDNA repair. Rather, it was the introduction of autoradiographic methods to study quantitatively the relative amounts of nDNA damage (measured as nDNA single-strand breaks) and nDNA repair (measured as unscheduled DNA synthesis) on tissue sections that made it possible to address this question in a cell-type-specific manner under physiological conditions. The results of these studies revealed a formerly unknown inverse relationship between age-related accumulation of nDNA damage and age-related impairment in nDNA repair on the one hand, and the age-related, selective, loss of neurons on the other hand. This inverse relation may not only reflect a fundamental process of aging in the central nervous system but also provide the molecular basis for a new approach to understand the selective neuronal vulnerability in neurodegenerative diseases, particularly Alzheimer's disease. 相似文献