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51.
Amyloid precursor protein (APP) is a type 1 transmembrane glycoprotein, and its homologs amyloid precursor-like protein 1 (APLP1) and amyloid precursor-like protein 2 (APLP2) are highly conserved in mammals. APP and APLP are known to be intimately involved in the pathogenesis and progression of Alzheimer’s disease and to play important roles in neuronal homeostasis and development and neural transmission. APP and APLP are also expressed in non-neuronal tissues and are overexpressed in cancer cells. Furthermore, research indicates they are involved in several cancers. In this review, we examine the biological characteristics of APP-related family members and their roles in cancer. 相似文献
52.
Katarzyna Chamera Ewa Trojan Katarzyna Kotarska Magdalena Szuster-Guszczak Natalia Bryniarska Kinga Tylek Agnieszka Basta-Kaim 《International journal of molecular sciences》2021,22(4)
Multiple lines of evidence support the pathogenic role of maternal immune activation (MIA) in the occurrence of the schizophrenia-like disturbances in offspring. While in the brain the homeostatic role of neuron-microglia protein systems is well documented, the participation of the CX3CL1-CX3CR1 and CD200-CD200R dyads in the adverse impact of MIA often goes under-recognized. Therefore, in the present study, we examined the effect of MIA induced by polyinosinic:polycytidylic acid (Poly I:C) on the CX3CL1-CX3CR1 and CD200-CD200R axes, microglial trajectory (MhcII, Cd40, iNos, Il-1β, Tnf-α, Il-6, Arg1, Igf-1, Tgf-β and Il-4), and schizophrenia-like behaviour in adult male offspring of Sprague-Dawley rats. Additionally, according to the “two-hit” hypothesis of schizophrenia, we evaluated the influence of acute challenge with Poly I:C in adult prenatally MIA-exposed animals on the above parameters. In the present study, MIA evoked by Poly I:C injection in the late period of gestation led to the appearance of schizophrenia-like disturbances in adult offspring. Our results revealed the deficits manifested as a diminished number of aggressive interactions, presence of depressive-like episodes, and increase of exploratory activity, as well as a dichotomy in the sensorimotor gating in the prepulse inhibition (PPI) test expressed as two behavioural phenotypes (MIAPPI-low and MIAPPI-high). Furthermore, in the offspring rats subjected to a prenatal challenge (i.e., MIA) we noticed the lack of modulation of behavioural changes after the additional acute immune stimulus (Poly I:C) in adulthood. The important finding reported in this article is that MIA affects the expression and levels of the neuron-microglia proteins in the frontal cortex and hippocampus of adult offspring. We found that the changes in the CX3CL1-CX3CR1 axis could affect microglial trajectory, including decreased hippocampal mRNA level of MhcII and elevated cortical expression of Igf-1 in the MIAPPI-high animals and/or could cause the up-regulation of an inflammatory response (Il-6, Tnf-α, iNos) after the “second hit” in both examined brain regions and, at least in part, might differentiate behavioural disturbances in adult offspring. Consequently, the future effort to identify the biological background of these interactions in the Poly I:C-induced MIA model in Sprague-Dawley rats is desirable to unequivocally clarify this issue. 相似文献
53.
54.
Accurate measurements of radiation dose are essential prerequisites for the safe and effective use of ionizing radiation in diagnostic and therapeutic medical applications. Recently, dosimeters based on organic polymers have been developed for this purpose. In this work, Poly(3-hexylthiophene-2,5-diyl) (P3HT) based organic diodes were evaluated as potential radiation dosimeters by quantifying the radiation-induced photocurrent under various measurement conditions. Control devices were fabricated in which the P3HT was replaced by polystyrene (PS) for the purpose of quantifying the non-photocurrent contribution to the measured signal. Net photocurrent was determined by subtracting the signal from the PS devices from the signal in the P3HT devices under identical measurement conditions. The responses of these devices were tested in various beam qualities: 100 kVp, 180 kVp, 300 kVp and 6 MV, 18 MV photons. The influences of electric field, film thickness and dose rate on dosimeter sensitivity were investigated. The diodes produced a linear increase in current with increasing dose rate. They demonstrated an increase in sensitivity with increased instantaneous dose rate and an increase in sensitivity at the lowest average dose rates studied here. The sensitivities for different energies were 22.9 nC/Gy, 21.8 nC/Gy and 21.4 nC/Gy for 100 kVp, 180 kVp and 300 kVp, respectively; and 14.5 nC/Gy, 14.7 nC/Gy for 6 MV and 18 MV, respectively for device with P3HT thickness 29 μm. 相似文献
55.
Daisuke Yamanaka Suzuka Kurita Yuka Hanayama Yoshiyuki Adachi 《International journal of molecular sciences》2021,22(4)
β-Glucan is widely distributed in various plants and microorganisms and is composed of β-1,3-linked d-glucose units. It may have a branched short or long side chain of glucose units with β-1,6- or β-1,4-linkage. Numerous studies have investigated different β-glucans and revealed their bioactivities. To understand the structure-function relationship of β-glucan, we constructed a split-luciferase complementation assay for the structural analysis of long-chain β-1,6-branched β-1,3-glucan. The N- and C-terminal fragments of luciferase from deep-sea shrimp were fused to insect-derived β-1,3-glucan recognition protein and fungal endo-β-1,6-glucanase (Neg1)-derived β-1,6-glucan recognition protein, respectively. In this approach, two β-glucan recognition proteins bound to β-glucan molecules come into close proximity, resulting in the assembly of the full-length reporter enzyme and induction of transient luciferase activity, indicative of the structure of β-glucan. To test the applicability of this assay, β-glucan and two β-glucan recognition proteins were mixed, resulting in an increase in the luminescence intensity in a β-1,3-glucan with a long polymer of β-1,6-glucan in a dose-dependent manner. This simple test also allows the monitoring of real-time changes in the side chain structure and serves as a convenient method to distinguish between β-1,3-glucan and long-chain β-1,6-branched β-1,3-glucan in various soluble and insoluble β-glucans. 相似文献
56.
57.
周家荣 《电信工程技术与标准化》2021,34(9)
移动边缘云是公司“云+5G”双引擎战略的最佳契合点,边缘网络是发挥移动云“大云”产品和5G网络融合优势,实现云网统筹、构建运营商“连接+计算”核心能力的关键。运营商传统接入网存在云网割裂、分段入云和组网复杂等突出问题,难以适应边缘业务敏捷交付要求。本文通过深入分析边缘云业务特征和技术架构,对标业界主流云商建设实践,研究基于云网PoP网的边缘网络建设思路,创新性提出云网一体化规划设计和建设交付流程变革,基于云网POP统一网络和业务锚点,构建Overlay和Underlay融合双层加速网络架构,探索Spine-leaf化的新型城域接入网实现L3下沉和弹性扩容等方法,实现“云+网+应用”一体化敏捷交付的边缘网络能力。 相似文献
58.
Ruirui Lu Katharina Metzner Fangyuan Zhou Cathrin Flauaus Annika Balzulat Patrick Engel Jonas Petersen Rebekka Ehinger Anne Bausch Peter Ruth Robert Lukowski Achim Schmidtko 《International journal of molecular sciences》2021,22(1)
The sodium-activated potassium channel Slack (KNa1.1, Slo2.2, or Kcnt1) is highly expressed in populations of sensory neurons, where it mediates the sodium-activated potassium current (IKNa) and modulates neuronal activity. Previous studies suggest that Slack is involved in the processing of neuropathic pain. However, mechanisms underlying the regulation of Slack activity in this context are poorly understood. Using whole-cell patch-clamp recordings we found that Slack-mediated IKNa in sensory neurons of mice is reduced after peripheral nerve injury, thereby contributing to neuropathic pain hypersensitivity. Interestingly, Slack is closely associated with ATP-sensitive P2X3 receptors in a population of sensory neurons. In vitro experiments revealed that Slack-mediated IKNa may be bidirectionally modulated in response to P2X3 activation. Moreover, mice lacking Slack show altered nocifensive responses to P2X3 stimulation. Our study identifies P2X3/Slack signaling as a mechanism contributing to hypersensitivity after peripheral nerve injury and proposes a potential novel strategy for treatment of neuropathic pain. 相似文献
59.
Saerom Lee Ga-Eun Lim Yong-Nyun Kim Hyeon-Sook Koo Jaegal Shim 《International journal of molecular sciences》2021,22(4)
The extracellular matrix (ECM) is important for normal development and disease states, including inflammation and fibrosis. To understand the complex regulation of ECM, we performed a suppressor screening using Caenorhabditis elegans expressing the mutant ROL-6 collagen protein. One cuticle mutant has a mutation in dpy-23 that encodes the μ2 adaptin (AP2M1) of clathrin-associated protein complex II (AP-2). The subsequent suppressor screening for dpy-23 revealed the lon-2 mutation. LON-2 functions to regulate body size through negative regulation of the tumor growth factor-beta (TGF-β) signaling pathway responsible for ECM production. RNA-seq analysis showed a dominant change in the expression of collagen genes and cuticle components. We noted an increase in the cav-1 gene encoding caveolin-1, which functions in clathrin-independent endocytosis. By knockdown of cav-1, the reduced TGF-β signal was significantly restored in the dpy-23 mutant. In conclusion, the dpy-23 mutation upregulated cav-1 expression in the hypodermis, and increased CAV-1 resulted in a decrease of TβRI. Finally, the reduction of collagen expression including rol-6 by the reduced TGF-β signal influenced the cuticle formation of the dpy-23 mutant. These findings could help us to understand the complex process of ECM regulation in organism development and disease conditions. 相似文献
60.
Maria Rita Gulotta Serena Vittorio Rosaria Gitto Ugo Perricone Laura De Luca 《International journal of molecular sciences》2021,22(4)
The modulation of protein-protein interactions (PPIs) by small molecules represents a valuable strategy for pharmacological intervention in several human diseases. In this context, computer-aided drug discovery techniques offer useful resources to predict the network of interactions governing the recognition process between protein partners, thus furnishing relevant information for the design of novel PPI modulators. In this work, we focused our attention on the MUC1-CIN85 complex as a crucial PPI controlling cancer progression and metastasis. MUC1 is a transmembrane glycoprotein whose extracellular domain contains a variable number of tandem repeats (VNTRs) regions that are highly glycosylated in normal cells and under-glycosylated in cancer. The hypo-glycosylation fosters the exposure of the backbone to new interactions with other proteins, such as CIN85, that alter the intracellular signalling in tumour cells. Herein, different computational approaches were combined to investigate the molecular recognition pattern of MUC1-CIN85 PPI thus unveiling new structural information useful for the design of MUC1-CIN85 PPI inhibitors as potential anti-metastatic agents. 相似文献