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111.
Lo WY Botzolakis EJ Tang X Macdonald RL 《The Journal of biological chemistry》2008,283(44):29740-29752
Members of the Cys-loop superfamily of ligand-gated ion channels, which mediate fast synaptic transmission in the nervous system, are assembled as heteropentamers from a large repertoire of neuronal subunits. Although several motifs in subunit N-terminal domains are known to be important for subunit assembly, increasing evidence points toward a role for C-terminal domains. Using a combination of flow cytometry, patch clamp recording, endoglycosidase H digestion, brefeldin A treatment, and analytic centrifugation, we identified a highly conserved aspartate residue at the boundary of the M3-M4 loop and the M4 domain that was required for binary and ternary gamma-aminobutyric acid type A receptor surface expression. Mutation of this residue caused mutant and partnering subunits to be retained in the endoplasmic reticulum, reflecting impaired forward trafficking. Interestingly although mutant and partnering wild type subunits could be coimmunoprecipitated, analytic centrifugation studies demonstrated decreased formation of pentameric receptors, suggesting that this residue played an important role in later steps of subunit oligomerization. We thus conclude that C-terminal motifs are also important determinants of Cys-loop receptor assembly. 相似文献
112.
The ethoxy chains of short ethoxy chain nonylphenol (NPEOav2.0, containing average 2.0 ethoxy units) were dehydrogenated by cell-free extracts from Ensifer sp. strain AS08 grown on a basal medium supplemented with NPEOav2.0. The reaction was coupled with the reduction in 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide and phenazine
methosulfate. The enzyme (NPEOav2.0 dehydrogenase; NPEO-DH) was purified to homogeneity with a yield of 20% and a 56-fold increase in specific activity. The
molecular mass of the native enzyme was 120 kDa, consisting of two identical monomer units (60 kDa). The gene encoding NPEO-DH
was cloned, which consisted of 1,659 bp, corresponding to a protein of 553 amino acid residues. The deduced amino acid sequence
agreed with the N-terminal amino acid sequence of the purified NPEO-DH. The presence of a flavin adenine dinucleotide (FAD)-binding
motif and glucose–methanol–choline (GMC) oxidoreductase signature motifs strongly suggested that the enzyme belongs to the
GMC oxidoreductase family. The protein exhibited homology (40–45% identity) with several polyethylene glycol dehydrogenases
(PEG-DHs) of this family, but the identity was lower than those (approximately 58%) among known PEG-DHs. The substrate-binding
domain was more hydrophobic compared with those of glucose oxidase and PEG-DHs. The recombinant protein had the same molecular
mass as the purified NPEO-DH and dehydrogenated PEG400-2000, NPEOav2.0 and its components, and NPEOav10, but only slight or no activity was found using diethylene glycol, triethylene glycol, and
PEG200.
English edition: The paper was edited by a native speaker through American Journal Experts (). 相似文献
113.
114.
Xin Hu Milos Vujanac Noel Southall C. Erec Stebbins 《Bioorganic & medicinal chemistry letters》2013,23(4):1056-1062
The bacterial protein tyrosine phosphatase YopH is an essential virulence determinant in Yersinia pestis and a potential antibacterial drug target. Here we report our studies of screening for small molecule inhibitors of YopH using both high throughput and in silico approaches. The identified inhibitors represent a diversity of chemotypes and novel pTyr mimetics, providing a starting point for further development and fragment-based design of multi-site binding inhibitors. We demonstrate that the applications of high throughput and virtual screening, when guided by structural binding mode analysis, is an effective approach for identifying potent and selective inhibitors of YopH and other protein phosphatases for rational drug design. 相似文献
115.
Aim
The aim of this study was to investigate the prevalence of interankle systolic blood pressure difference (sIAND) and its influencing factors in community population.Methods
This study included 2849 (65.1±9.4 y) subjects. Blood pressure (BPs) of four limbs was simultaneously measured with 4 electronic sphygmomanometers after 10 min rest in supine position. The difference of systolic BP (SBP) between two ankles was calculated as DETASBP. The criterion for abnormal sIAND was ≥10 mmHg of absolute DeltaSBP, in which the criterion for 1o sIAND was 10–19 mmHg and for 2o sIAND was ≥20 mmHg. Age, gender, smoking, hypertension, family histories of hypertension and diabetes were recorded. Fasting blood glucose and lipids, circumference of hip and waist, and body mass index (BMI) were measured.Results
The SBP was higher in the right ankle than in the left ankle (158.9±21.8 vs 157.3±21.6 mmHg, P<0.05) and mean DeltaSBP was 6.08±6.26 mmHg. Similar difference was found in both genders. The prevalence of abnormal was 18.5%, in which, the prevalence 1o sIAND was 15.3% and that of 2o sIAND was 3.1%. Multivariate regression analysis showed that age, waist circumference and blood glucose level were the positive factors for DeltaSBP. The normal upper limit for DeltaSBP was 16.7 mmHg in this population, the prevalence of sIAND by≥16 mmHg was 5.8%.Conclusion
Aging, hypertension, obesity and abnormal glucose metabolism are positive factors for inter-ankle SBP difference. 相似文献116.
Dola Das Ehsan Fayazzadeh Xin Li Nischal Koirala Akshay Wadera Min Lang Maximilian Zernic Catherine Panick Pete Nesbitt Gordon McLennan 《Journal of cellular physiology》2020,235(9):6167-6182
Hepatocellular carcinoma (HCC) is a major health problem worldwide and in the United States as its incidence has increased substantially within the past two decades. HCC therapy remains a challenge, primarily due to underlying liver disorders such as cirrhosis that determines treatment approach and efficacy. Activated hepatic stellate cells (A-HSCs) are the key cell types involved in hepatic fibrosis/cirrhosis. A-HSCs are important constituents of HCC tumor microenvironment (TME) and support tumor growth, chemotherapy resistance, cancer cell migration, and escaping immune surveillance. This makes A-HSCs an important therapeutic target in hepatic fibrosis/cirrhosis as well as in HCC. Although many studies have reported the role of A-HSCs in cancer generation and investigated the therapeutic potential of A-HSCs reversion in cancer arrest, not much is known about inactivated or quiescent HSCs (Q-HSCs) in cancer growth or arrest. Here we report that Q-HSCs resist cancer cell growth by inducing cytotoxicity and enhancing chemotherapy sensitivity. We observed that the conditioned media from Q-HSCs (Q-HSCCM) induces cancer cell death through a caspase-independent mechanism that involves an increase in apoptosis-inducing factor expression, nuclear localization, DNA fragmentation, and cell death. We further observed that Q-HSCCM enhanced the efficiency of doxorubicin, as measured by cell viability assay. Exosomes present in the conditioned media were not involved in the mechanism, which suggests the role of other factors (proteins, metabolites, or microRNA) secreted by the cells. Identification and characterization of these factors are important in the development of effective HCC therapy. 相似文献
117.
118.
Jin-Yong He Xiao-Hui Wei Si-Jing Li Yang Liu Hao-Lin Hu Zheng-Zheng Li Xin-Hong Kuang Lai Wang Xin Shi Sheng-Tao Yuan Li Sun 《Cell communication and signaling : CCS》2018,16(1):100
Background
Adipocytes make up the major component of breast tissue, accounting for 90% of stromal tissue. Thus, the crosstalk between adipocytes and breast cancer cells may play a critical role in cancer progression. Adipocyte-breast cancer interactions have been considered important for the promotion of breast cancer metastasis. However, the specific mechanisms underlying these interactions are unclear. In this study, we investigated the mechanisms of adipocyte-mediated breast cancer metastasis.Methods
Breast cancer cells were cocultured with mature adipocytes for migration and 3D matrix invasion assays. Next, lentivirus-mediated loss-of-function experiments were used to explore the function of lysyl hydroxylase (PLOD2) in breast cancer migration and adipocyte-dependent migration of breast cancer cells. The role of PLOD2 in breast cancer metastasis was further confirmed using orthotopic mammary fat pad xenografts in vivo. Clinical samples were used to confirm that PLOD2 expression is increased in tumor tissue and is associated with poor prognosis of breast cancer patients. Cells were treated with cytokines and pharmacological inhibitors in order to verify which adipokines were responsible for activation of PLOD2 expression and which signaling pathways were activated in vitro.Results
Gene expression profiling and Western blotting analyses revealed that PLOD2 was upregulated in breast cancer cells following coculture with adipocytes; this process was accompanied by enhanced breast cancer cell migration and invasion. Loss-of-function studies indicated that PLOD2 knockdown suppressed cell migration and disrupted the formation of actin stress fibers in breast cancer cells and abrogated the migration induced by following coculture with adipocytes. Moreover, experiments performed in orthotopic mammary fat pad xenografts showed that PLOD2 knockdown could reduce metastasis to the lung and liver. Further, high PLOD2 expression correlated with poor prognosis of breast cancer patients. Mechanistically, adipocyte-derived interleukin-6 (IL-6) and leptin may facilitate PLOD2 upregulation in breast cancer cells and promote breast cancer metastasis in tail vein metastasis assays. Further investigation revealed that adipocyte-derived IL-6 and leptin promoted PLOD2 expression through activation of the JAK/STAT3 and PI3K/AKT signaling pathways.Conclusions
Our study reveals that adipocyte-derived IL-6 and leptin promote PLOD2 expression by activating the JAK/STAT3 and PI3K/AKT signaling pathways, thus promoting breast cancer metastasis.119.
以HeLa细胞和BALB/c小鼠为模型,研究了高压力对柯萨B组病毒(CVB)感染活性和免疫原性的影响,发现在230MPa压力下,结合其他相应的物理条件,CVB的感染活性可完全消失。该CVB仍具有抗原性,可诱导小鼠产生CVB特异性抗性,效价可达1:1500。用高压力处理的CVB免疫小鼠,再用正常CVB攻击,其生存率为67%,具有疫苗的特性。这些结果表明,高压力处理的CVB具有免疫保护作用,可作为一种具有潜在应用前景的病毒疫苗。 相似文献
120.
黄土高原小流域景观多样性动态分析 总被引:15,自引:6,他引:15
以纸坊沟为例,在地理信息系统支持下获得计算景观多样性的有关参数,运用斑块大小及数量、平均分维数、多样性指数、优势度、均匀度、破碎度和聚集度等指标,对黄土高原小流域40年来景观多样性动态变化进行了分析.结果表明,40年来,在以人类活动干预和植被内源演替为主要驱动力的共同作用下,该流域斑块总数增加,旱地基质逐渐被林地、草地等其它景观基质所取代,景观格局趋于破碎,景观类型多样性和均匀度增加,且后20年景观多样性的变化幅度远远大于前20年的变化幅度.目前流域已经由1958年以旱地为基质的高度均质化的景观生态系统转化为与当地地带性景观相适应的以草地和林地为基质的高度异质化的景观生态系统,生态系统结构、功能已具有较强的稳定性. 相似文献