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991.
Comparative molecular surface analysis (CoMSA) with robust IVE-PLS variable elimination if tested for the benchmark CBG steroid
series provides highly predictive RI 3D QSAR models, but failed however to model the activity of sulforaphane (SP) activators
of quinone reductase. The application of the SP poses obtained from multipose molecular docking to model the RD IVE-PLS CoMSA
resulted in a predictive form. This model indicated lipophilic potential as the activity determinant. The individual molecular
surface areas of the highest contribution to the SP activity was identified and visualized by CoMSA contour plots. 相似文献
992.
Xiaoyu Wang Lianli Sun Kexin Huang Shuyun Shi Lijuan Zhang Juanhua Xu Hua Peng Xianfeng Sun Liwei Wang Xiumei Wu Yu Zhao Xiaokun Li Joachim Stöckigt Jia Qu 《化学与生物多样性》2009,6(7):1053-1065
A phytochemical investigation of the roots of Ligularia atroviolacea resulted in the isolation of 24 compounds including seven new eremophilanoids named eremophila‐3,7(11),8‐triene‐12,8;14,6α‐diolide ( 1 ), 3β‐(angeloyloxy)eremophil‐7(11)‐en‐12,8β‐olid‐14‐oic acid ( 2 ), 1α‐chloro‐10β‐hydroxy‐6β‐(2‐methylpropanoyloxy)‐9‐oxo‐7,8‐furoeremophilane ( 3 ), (10βH)‐8‐oxoeremophila‐3(4),6(7)‐diene‐12,14‐dioic acid ( 4 ), (10αH)‐8‐oxoeremophila‐3(4),6(7)‐diene‐12,14‐dioic acid ( 5 ), 8β‐[eremophila‐3′,7′(11′)‐diene‐12′,8′α;14′,6′α‐diolide]eremophila‐3,7(11)‐diene‐12,8α;14,6α‐diolide ( 6 ), and ligulatrovine A ( 7 ), eleven known eremophilanoids, 8 – 18 , four steroids, one glucose derivative, and one fatty acid. The structures of these compounds were elucidated by spectroscopic methods including 2D‐NMR experiments. The structure of 3 was also established by an X‐ray diffraction study. The in vitro cytotoxicity evaluation of selected compounds was performed on seven cultured tumor cell lines, i.e., KB, BEL‐7404, A549, HL‐60, HeLa, CNE, and P‐388D1. The preliminary taxonomy of this species was also discussed, and the possible biogenesis of a dimer possessing a new noreremophilanoid type skeleton, 7 , is presented in a preliminary form. 相似文献
993.
Ligia Subitoni Antonio Roberta Ribeiro Costa Marcelo Damário Gomes Wamberto Antonio Varanda 《Purinergic signalling》2009,5(3):277-287
ATP acts on cellular membranes by interacting with P2X (ionotropic) and P2Y (metabotropic) receptors. Seven homomeric P2X
receptors (P2X1–P2X7) and seven heteromeric receptors (P2X1/2, P2X1/4, P2X1/5, P2X2/3, P2X2/6, P2X4/6, P2X4/7) have been described. ATP treatment of Leydig cells leads to an increase in [Ca2+]i and testosterone secretion, supporting the hypothesis that Ca2+ signaling through purinergic receptors contributes to the process of testosterone secretion in these cells. Mouse Leydig
cells have P2X receptors with a pharmacological and biophysical profile resembling P2X2. In this work, we describe the presence of several P2X receptor subunits in mouse Leydig cells. Western blot experiments
showed the presence of P2X2, P2X4, P2X6, and P2X7 subunits. These results were confirmed by immunofluorescence. Functional results support the hypothesis that heteromeric
receptors are present in these cells since 0.5 μM ivermectin induced an increase (131.2 ± 5.9%) and 3 μM ivermectin a decrease
(64.2 ± 4.8%) in the whole-cell currents evoked by ATP. These results indicate the presence of functional P2X4 subunits. P2X7 receptors were also present, but they were non-functional under the present conditions because dye uptake experiments with
Lucifer yellow and ethidium bromide were negative. We conclude that a heteromeric channel, possibly P2X2/4/6, is present in Leydig cells, but with an electrophysiological and pharmacological phenotype characteristic of the P2X2 subunit. 相似文献
994.
杏属(蔷薇科)一新种 总被引:2,自引:0,他引:2
发表了蔷薇科杏属的一个新种,即仙居杏(Armeniaca Xianjuxing J.Y.Zhang et Z.X.Wu),其与普通杏(Armeniaca vulgaris Lam.)的区别在于叶片两面具有短柔毛,花梗或果梗长1~1.2 cm,花瓣边缘钝锯齿或小裂片状,萼片边缘有小钝锯齿。 相似文献
995.
Hepatic parenchymal and nonparenchymal cells are highly susceptible to ethanol and its metabolites, and excessive alcohol consumption results in damage to the liver. Ethanol induces an increased prevalence for bacterial overgrowth in the small intestine and translocation of endotoxin into the portal blood. Some studies have pointed to a role for activation of Kupffer cells by gut bacteria-derived endotoxin as a primary event in mechanisms of alcoholic liver injury (ALD). GW4064, a potent farnesoid X receptor (FXR) agonist, has been developed as a hepatoprotective agent, and has been used in animal models of a variety of liver diseases. At the same time, previous experimental results showed that BAs and GW4064 inhibit bacterial overgrowth in the small intestine. It is logical to postulate that GW4064 may control or alleviate the ethanol-induced liver injury through inhibiting gut bacterial overgrowth. GW4064 activates FXR, which induces the expression of several genes with potential functions in mucosal defense to prevent intestinal bacteria overgrowth and translocation into the circulation induced by ethanol, and then will alleviate ethanol-induced liver injury. The hypothesis will provide the brand-new direction that we may prevent and treat ALD by using GW4064 through activating FXR to control gut bacteria overgrowth. 相似文献
996.
997.
998.
Raffaella M. Gadaleta Saskia W.C. van Mil Bas Oldenburg Peter D. Siersema Leo W.J. Klomp Karel J. van Erpecum 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2010,1801(7):683-692
The nuclear receptor Farnesoid X Receptor (FXR) critically regulates nascent bile formation and bile acid enterohepatic circulation. Bile acids and FXR play a pivotal role in regulating hepatic inflammation and regeneration as well as in regulating extent of inflammatory responses, barrier function and prevention of bacterial translocation in the intestinal tract. Recent evidence suggests, that the bile acid–FXR interaction is involved in the pathophysiology of a wide range of diseases of the liver, biliary and gastrointestinal tract, such as cholestatic and inflammatory liver diseases and hepatocellular carcinoma, inflammatory bowel disease and inflammation-associated cancer of the colon and esophagus. In this review we discuss current knowledge of the role the bile acid–FXR interaction has in (patho)physiology of the liver, biliary and gastrointestinal tract, and proposed underlying mechanisms, based on in vitro data and experimental animal models. Given the availability of highly potent synthetic FXR agonists, we focus particularly on potential relevance for human disease. 相似文献
999.
Development of dry powder inhalation system of novel vasoactive intestinal peptide (VIP) analogue for pulmonary administration 总被引:2,自引:0,他引:2
Vasoactive intestinal peptide (VIP) exerts a relaxing action on tracheal smooth muscle which is mediated through interaction with VIP receptors. The deficiency of VIP in the airways has been implicated in the pathogenesis of asthma. Thus, the administration of VIP may be useful for the therapy of pulmonary diseases. However, the therapeutic application of VIP is largely limited by its rapid degradation in addition to the systemic adverse effects due to the wide distribution of VIP receptors. To overcome these problems, we succeeded to synthesize a novel VIP derivative of VIP, [R15, 20, 21, L17]-VIP-GRR (IK312532), and to prepare its dry powder for the topical administration to the lung. The physicochemical properties of dry powder were evaluated by laser diffraction and cascade impactor. The laser diffraction analysis indicated that the carrier and fine particles had median diameter of 65.6 and 4.5 microm, respectively, and the air flow at the pressure of 0.15 MPa or higher resulted in the high dispersion and significant separation of fine particle containing peptide from the carrier molecule. The cascade impactor analysis clearly showed the high emission of dry powder from capsule and the deposition of peptide on stages 3 of the cascade impactor. The intratracheal administration of dry powder inhaler (DPI) of VIP or IK312532 brought about a significant decrease of maximal number of binding sites (Bmax) for [125I]VIP in anterior and posterior lobes of rat right lung, suggesting a significant occupancy of lung VIP receptors. This effect by IK312532-DPI compared with VIP-DPI lasted for a longer period. Thus, IK312532-DPI may be a pharmacologically useful drug delivery system for the VIP therapy of pulmonary diseases such as asthma. 相似文献
1000.