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101.
Rong‐rong Zhu Qian Chen Zhi‐bo Liu Han‐guang Ruan Qi‐cai Wu Xue‐liang Zhou 《Journal of cellular and molecular medicine》2020,24(14):7907-7914
Increased expression and activity of cardiac and circulating cathepsin D and soluble fms‐like tyrosine kinase‐1 (sFlt‐1) have been demonstrated to induce and promote peripartum cardiomyopathy (PPCM) via promoting cleavage of 23‐kD prolactin (PRL) to 16‐kD PRL and neutralizing vascular endothelial growth factor (VEGF), respectively. We hypothesized that activation of Hes1 is proposed to suppress cathepsin D via activating Stat3, leading to alleviated development of PPCM. In the present study, we aimed to investigate the role of Notch1/Hes1 pathway in PPCM. Pregnant mice between prenatal 3 days and postpartum 3 weeks were fed with LY‐411575 (a notch inhibitor, 10 mg/kg/d). Ventricular function and pathology were evaluated by echocardiography and histological analysis. Western blotting analysis was used to examine the expression at the protein level. The results found that inhibition of Notch1 significantly promoted postpartum ventricular dilatation, myocardial hypertrophy and myocardial interstitial fibrosis and suppressed myocardial angiogenesis. Western blotting analysis showed that inhibition of Notch1 markedly increased cathepsin D and sFlt‐1, reduced Hes1, phosphorylated Stat3 (p‐Stat3), VEGFA and PDGFB, and promoted cleavage of 23k‐D PRL to 16‐kD PRL. Collectively, inhibition of Notch1/Hes1 pathway induced and promoted PPCM via increasing the expressions of cathepsin D and sFlt‐1. Notch1/Hes1 was a promising target for prevention and therapeutic regimen of PPCM. 相似文献
102.
Zhi Qian Zeyuan Zhong Shuo Ni Dejian Li Fangxue Zhang Ying Zhou Zhanrong Kang Jun Qian Baoqing Yu 《Journal of cellular and molecular medicine》2020,24(17):10112-10127
Postmenopausal Osteoporosis (PMOP) is oestrogen withdrawal characterized of much production and activation by osteoclast in the elderly female. Cytisine is a quinolizidine alkaloid that comes from seeds or other plants of the Leguminosae (Fabaceae) family. Cytisine has been shown several potential pharmacological functions. However, its effects on PMOP remain unknown. This study designed to explore whether Cytisine is able to suppress RANKL‐induced osteoclastogenesis and prevent the bone loss induced by oestrogen deficiency in ovariectomized (OVX) mice. In this study, we investigated the effect of Cytisine on RAW 264.7 cells and bone marrow monocytes (BMMs) derived osteoclast culture system in vitro and observed the effect of Cytisine on ovariectomized (OVX) mice model to imitate postmenopausal osteoporosis in vivo. We found that Cytisine inhibited F‐actin ring formation and tartrate‐resistant acid phosphatase (TRAP) staining in dose‐dependent ways, as well as bone resorption by pit formation assays. For molecular mechanism, Cytisine suppressed RANK‐related trigger RANKL by phosphorylation JNK/ERK/p38‐MAPK, IκBα/p65‐NF‐κB, and PI3K/AKT axis and significantly inhibited these signalling pathways. However, the suppression of PI3K‐AKT‐NFATc1 axis was rescued by AKT activator SC79. Meanwhile, Cytisine inhibited RANKL‐induced RANK‐TRAF6 association and RANKL‐related gene and protein markers such as NFATc1, Cathepsin K, MMP‐9 and TRAP. Our study indicated that Cytisine could suppress bone loss in OVX mouse through inhibited osteoclastogenesis. All data provide the evidence that Cytisine may be a promising agent in the treatment of osteoclast‐related diseases such as osteoporosis. 相似文献
103.
104.
Weixiang He Jianmin Liu Daoquan Liu Jundong Hu Ye Jiang Mingzhou Li Qian Wang Ping Chen Guang Zeng Deqiang Xu Xinghuan Wang Michael E. DiSanto Xinhua Zhang 《Journal of cellular and molecular medicine》2020,24(24):14280
To explore how alterations in the phosphodiesterase type 5 (PDE5) signalling pathway and oxidative stress correlate with changes in the expression of relaxation and contraction molecules and erectile dysfunction (ED) in the corpus cavernosum smooth muscle (CCSM) of spontaneously hypertensive rats (SHR). In this study, SHR and Wistar‐Kyoto (WKY) rats were used. Erectile function was determined by apomorphine test and electrical stimulation (ES) of cavernous nerve. Masson''s trichrome staining and confocal microscopy were performed. Nitric oxide synthase (NOS), PDE5, phosphorylated‐PDE5 and α1‐adrenergic receptor (α1AR) were determined by RT‐PCR and Western blotting while oxidative stress in CC was determined by colorimetric analysis. SHR exhibited obvious ED. CC of SHR showed less SM but more collagen fibres. The expression of NOS isoforms in SHR was significantly decreased while all α1AR isoforms were increased. In addition, PDE5 and phosphorylated‐PDE5 were down‐regulated and its activity attenuated in the hypertensive rats. Meanwhile, the SHR group suffered oxidative stress, which may be modulated by endoplasmic reticulum stress and NADPH oxidase up‐regulation. Dysregulation of NOS and α1AR, histological changes and oxidative stress in CC may be associated with the pathophysiology of hypertension‐induced ED. In addition, PDE5 down‐regulation may lead to the decreased efficacy of PDE5 inhibitors in some hypertensive ED patients and treatment of oxidative stress could be used as a new therapeutic target for this type of ED. 相似文献
105.
Hao Chen Peng Tan Baolin Qian Yichao Du Ankang Wang Hao Shi Zhiwei Huang Shiyao Huang Tiancheng Liang Wenguang Fu 《Journal of cellular and molecular medicine》2020,24(2):1488-1503
Chronic pancreatitis (CP), characterized by pancreatic fibrosis, is a recurrent, progressive and irreversible disease. Activation of the pancreatic stellate cells (PSCs) is considered a core event in pancreatic fibrosis. In this study, we investigated the role of hydrogen peroxide‐inducible clone‐5 (Hic‐5) in CP. Analysis of the human pancreatic tissue samples revealed that Hic‐5 was overexpressed in patients with CP and was extremely low in healthy pancreas. Hic‐5 was significant up‐regulated in the activated primary PSCs independently from transforming growth factor beta stimulation. CP induced by cerulein injection was ameliorated in Hic‐5 knockout (KO) mice, as shown by staining of tissue level. Simultaneously, the activation ability of the primary PSCs from Hic‐5 KO mice was significantly attenuated. We also found that the Hic‐5 up‐regulation by cerulein activated the NF‐κB (p65)/IL‐6 signalling pathway and regulated the downstream extracellular matrix (ECM) genes such as α‐SMA and Col1a1. Therefore, we determined whether suppressing NF‐κB/p65 alleviated CP by treating mice with the NF‐κB/p65 inhibitor triptolide in the cerulein‐induced CP model and found that pancreatic fibrosis was alleviated by NF‐κB/p65 inhibition. These findings provide evidence for Hic‐5 as a therapeutic target that plays a crucial role in regulating PSCs activation and pancreatic fibrosis. 相似文献
106.
Xin Li Chen Huang Cheng Liang Sui Chun Mei Liang Guang Ying Qi Qian Yao Ren Jian Chen Zhao Quan Huang 《Journal of cellular and molecular medicine》2020,24(1):875-885
Formononetin is a natural isoflavone compound found mainly in Chinese herbal medicines such as astragalus and red clover. It is considered to be a typical phytooestrogen. In our previous experiments, it was found that formononetin has a two‐way regulatory effect on endothelial cells (ECs): low concentrations promote the proliferation of ECs and high concentrations have an inhibitory effect. To find a specific mechanism of action and provide a better clinical effect, we performed a structural transformation of formononetin and selected better medicinal properties for formononetin modifier J1 and J2 from a variety of modified constructs. The MTT assay measured the effects of drugs on human umbilical vein endothelial cell (HUVEC) activity. Scratch and transwell experiments validated the effects of the drugs on HUVEC migration and invasion. An in vivo assessment effect of the drugs on ovariectomized rats. Long‐chain non‐coding RNA for EWSAT1, which is abnormally highly expressed in HUVEC, was screened by gene chip, and the effect of the drug on its expression was detected by PCR after the drug was applied. The downstream factors and their pathways were analysed, and the changes in the protein levels after drug treatment were evaluated by Western blot. In conclusion, the mechanism of action of formononetin, J1 and J2 on ECs may be through EWSAT1‐TRAF6 and its downstream pathways. 相似文献
107.
Wu‐Xia Qiu Xiao‐Li Ma Xiao Lin Fan Zhao Di‐Jie Li Zhi‐Hao Chen Ke‐Wen Zhang Ru Zhang Pai Wang Yun‐Yun Xiao Zhi‐Ping Miao Kai Dang Xiao‐Yang Wu Ai‐Rong Qian 《Journal of cellular and molecular medicine》2020,24(1):317-327
Microtubule actin cross‐linking factor 1 (Macf1) is a spectraplakin family member known to regulate cytoskeletal dynamics, cell migration, neuronal growth and cell signal transduction. We previously demonstrated that knockdown of Macf1 inhibited the differentiation of MC3T3‐E1 cell line. However, whether Macf1 could regulate bone formation in vivo is unclear. To study the function and mechanism of Macf1 in bone formation and osteogenic differentiation, we established osteoblast‐specific Osterix (Osx) promoter‐driven Macf1 conditional knockout mice (Macf1f/fOsx‐Cre). The Macf1f/fOsx‐Cre mice displayed delayed ossification and decreased bone mass. Morphological and mechanical studies showed deteriorated trabecular microarchitecture and impaired biomechanical strength of femur in Macf1f/fOsx‐Cre mice. In addition, the differentiation of primary osteoblasts isolated from calvaria was inhibited in Macf1f/fOsx‐Cre mice. Deficiency of Macf1 in primary osteoblasts inhibited the expression of osteogenic marker genes (Col1, Runx2 and Alp) and the number of mineralized nodules. Furthermore, deficiency of Macf1 attenuated Bmp2/Smad/Runx2 signalling in primary osteoblasts of Macf1f/fOsx‐Cre mice. Together, these results indicated that Macf1 plays a significant role in bone formation and osteoblast differentiation by regulating Bmp2/Smad/Runx2 pathway, suggesting that Macf1 might be a therapeutic target for bone disease. 相似文献
108.
Shuming Dou Jie Xu Xiaoya Cui Weidi Liu Zhicheng Zhang Yida Deng Wenbin Hu Yanan Chen 《Liver Transplantation》2020,10(33)
Functional nanomaterials are playing a crucial role in the emerging field of energy‐related devices. Recently, as a novel synthesis method, high‐temperature shock (HTS), which is rapid, low cost, eco‐friendly, universal, scalable, and controllable, has provided a promising option for the rational design and synthesis of various high‐quality nanomaterials. In this report, the HTS technique, including the equipment setup and operating principle, is systematically introduced, and recent progress in the synthesis of nanomaterials for energy storage and conversion applications using this HTS method is summarized. The growth mechanisms of nanoparticles and carbonaceous nanomaterials are thoroughly discussed, followed by the summary of the characteristic advantages of the HTS strategy. A series of nanomaterials prepared by the HTS method, including carbon‐based films, metal nanoparticles and compound nanoparticles, show high performance in the diverse applications of storage energy batteries, highly active catalysts, and smart energy devices. Finally, the future perspectives and directions of HTS in nanomanufacturing for broader applications are presented. 相似文献
109.
Xixi Wang Jaka Sunarso Qian Lu Ziling Zhou Jie Dai Daqin Guan Wei Zhou Zongping Shao 《Liver Transplantation》2020,10(5)
Constructing highly active electrocatalysts with superior stability at low cost is a must, and vital for the large‐scale application of rechargeable Zn–air batteries. Herein, a series of bifunctional composites with excellent electrochemical activity and durability based on platinum with the perovskite Sr(Co0.8Fe0.2)0.95P0.05O3?δ (SCFP) are synthesized via a facile but effective strategy. The optimal sample Pt‐SCFP/C‐12 exhibits outstanding bifunctional activity for the oxygen reduction reaction and oxygen evolution reaction with a potential difference of 0.73 V. Remarkably, the Zn–air battery based on this catalyst shows an initial discharge and charge potential of 1.25 and 2.02 V at 5 mA cm?2, accompanied by an excellent cycling stability. X‐ray photoelectron spectroscopy, X‐ray absorption near‐edge structure, and extended X‐ray absorption fine structure experiments demonstrate that the superior performance is due to the strong electronic interaction between Pt and SCFP that arises as a result of the rapid electron transfer via the Pt? O? Co bonds as well as the higher concentration of surface oxygen vacancies. Meanwhile, the spillover effect between Pt and SCFP also can increase more active sites via lowering energy barrier and change the rate‐determining step on the catalysts surface. Undoubtedly, this work provides an efficient approach for developing low‐cost and highly active catalysts for wider application of electrochemical energy devices. 相似文献
110.
Ya‐Qian Zhang Yaosen Tian Yihan Xiao Lincoln J. Miara Yuichi Aihara Tomoyuki Tsujimura Tan Shi M. C. Scott Gerbrand Ceder 《Liver Transplantation》2020,10(27)
The interfacial instability between a thiophosphate solid electrolyte and oxide cathodes results in rapid capacity fade and has driven the need for cathode coatings. In this work, the stability, evolution, and performance of uncoated, Li2ZrO3‐coated, and Li3B11O18‐coated LiNi0.5Co0.2Mn0.3O2 cathodes are compared using first‐principles computations and electron microscopy characterization. Li3B11O18 is identified as a superior coating that exhibits excellent oxidation/chemical stability, leading to substantially improved performance over cells with Li2ZrO3‐coated or uncoated cathodes. The chemical and structural origin of the different performance is interpreted using different microscopy techniques which enable the direct observation of the phase decomposition of the Li2ZrO3 coating. It is observed that Li is already extracted from the Li2ZrO3 in the first charge, leading to the formation of ZrO2 nanocrystallites with loss of protection of the cathode. After 50 cycles separated (Co, Ni)‐sulfides and Mn‐sulfides can be observed within the Li2ZrO3‐coated material. This work illustrates the severity of the interfacial reactions between a thiophosphate electrolyte and oxide cathode and shows the importance of using coating materials that are absolutely stable at high voltage. 相似文献