全文获取类型
收费全文 | 7331篇 |
免费 | 338篇 |
国内免费 | 298篇 |
专业分类
7967篇 |
出版年
2023年 | 83篇 |
2022年 | 156篇 |
2021年 | 169篇 |
2020年 | 232篇 |
2019年 | 323篇 |
2018年 | 323篇 |
2017年 | 221篇 |
2016年 | 226篇 |
2015年 | 185篇 |
2014年 | 446篇 |
2013年 | 706篇 |
2012年 | 216篇 |
2011年 | 425篇 |
2010年 | 253篇 |
2009年 | 305篇 |
2008年 | 320篇 |
2007年 | 345篇 |
2006年 | 277篇 |
2005年 | 305篇 |
2004年 | 264篇 |
2003年 | 244篇 |
2002年 | 206篇 |
2001年 | 127篇 |
2000年 | 105篇 |
1999年 | 113篇 |
1998年 | 113篇 |
1997年 | 118篇 |
1996年 | 131篇 |
1995年 | 97篇 |
1994年 | 79篇 |
1993年 | 91篇 |
1992年 | 77篇 |
1991年 | 71篇 |
1990年 | 36篇 |
1989年 | 50篇 |
1988年 | 34篇 |
1987年 | 40篇 |
1986年 | 31篇 |
1985年 | 42篇 |
1984年 | 77篇 |
1983年 | 41篇 |
1982年 | 57篇 |
1981年 | 33篇 |
1980年 | 41篇 |
1979年 | 38篇 |
1978年 | 11篇 |
1977年 | 19篇 |
1976年 | 15篇 |
1974年 | 18篇 |
1973年 | 14篇 |
排序方式: 共有7967条查询结果,搜索用时 15 毫秒
71.
Katsukawa H Shang Y Nakashima K Yang KH Ohashi R Sugita D Mishima K Nakata M Ninomiya Y Sugimura T 《Life sciences》2002,71(4):457-467
Dietary capsaicin consumed by rats over several days induces cystatin-like substances in submandibular saliva. Yet the physiological role of these salivary proteins has not been thoroughly investigated. Salivary cystatins in the rat submandibular glands are known to be induced by chronic treatment with the sympathetic beta-agonist, isoproterenol. In the present study, the possible roles of the salivary proteins on food intake were examined by comparing consumption of a capsaicin-adulterated (0.05%) diet in rats with and without isoproterenol pretreatment (0.1 and 5.0 mg/kg, 5 days). Electrophoretic analysis performed prior to feeding trials revealed that the group pretreated with 5 mg/kg isoproterenol had large amounts of cystatin in the saliva compared with the group pretreated with 0.1 mg/kg isoproterenol and control group. The group treated with 5 mg/kg isoproterenol showed greater consumption of the capsaicin-adulterated diet than the other groups until the 3rd day of trials. Bilateral removal of the submandibular and sublingual glands neutralized the effects of isoproterenol. Induction of salivary cystatins by isoproterenol treatment was not mimicked by systemic and intragastric administration of capsaicin. These results suggest that cystatins are included in the salivary proteins induced by capsaicin and that they contribute to enhanced ingestion of the capsaicin diet. Induction of salivary cystatins may be triggered by irritation of the oral mucosa by capsaicin. 相似文献
72.
核糖核酸酶抑制因子对H_2O_2损伤的大鼠神经胶质瘤细胞系C6的影响 总被引:2,自引:0,他引:2
核糖核酸酶抑制因子 (ribonucleaseinhibitor,RI)是广泛存在于哺乳动物细胞浆中的一种酸性糖蛋白 .为了进一步了解RI的功能 ,根据RI分子结构富含巯基的特点 ,研究了RI对过氧化氢(H2 O2 )损伤的大鼠神经胶质瘤细胞 (C6 )的影响 .用不同浓度的H2 O2 分别作用于转染有RIcDNA并且RI过表达的C6细胞和正常C6细胞 ,对比损伤前后 2者的细胞存活率、LDH漏出量、细胞内GSH和MDA含量差别 ,以及细胞内抗氧化酶类GPX、CAT和GST活性的差别 .结果表明 ,与正常C6细胞相比 ,RI过表达的C6细胞在H2 O2 作用下存活率高 ,LDH漏出量、MDA含量明显减少 ,而细胞内GSH较多 ;RI过表达的C6细胞在损伤前后均表现出更强的CAT和GST活性 .提示RI具有抗氧化功能 ,能够减轻H2 O2 所致的细胞过氧化损伤 . 相似文献
73.
Improved purification of potato tuber invertase was achieved by utilizing a form of affinity chromatography between the enzyme and Concanavalin A (Con A) bound to Sepharose. Twenty-fold increases in specific activity were routinely obtained with this step and the enzyme was purified 190-fold over that found in the crude homogenate. The Con A-Sepharose chromatography step gave a greater purification than any other step in the invertase isolation procedure. There was up to 170% recovery of the activity loaded onto the column. α-Methyl-d-mannoside, sucrose, d-glucose and d-fructose eluted the enzyme from the Con A-Sepharose column with similar recoveries, although the volume of eluent required varied with the sugar. This unusually high recovery of invertase activity was obtained with some batches of tubers but not with others. There was evidence to suggest that the high recovery, or activation, may be due to the release of an inhibitor from the enzyme in the presence of Con A-Sepharose. Adsorption of invertase to Con A-Sepharose could be eliminated by incubation of the enzyme with α-mannosidase and β-glucosidase, indicating that potato tuber invertase is a glycoprotein. Proteinaceous inhibitor purification was improved by treatment of the tuber extract at low pH. 相似文献
74.
Abdollahi M Bahreini-Moghadam A Emami B Fooladian F Zafari K 《Comparative biochemistry and physiology. Toxicology & pharmacology : CBP》2003,135(3):331-336
The effect of cadmium on induction of oxidative stress in rat submandibular saliva and protective role of increasing intracellular cAMP and cGMP by use of specific phosphodiesterase inhibitors, theophylline and sildenafil were investigated. Pure submandibular saliva was collected intraorally by micro polyethylene cannula from anaesthetized rats using pilocarpine as secretagogue. Acute administration of cadmium (10 mg/kg) caused significant oxidative stress by increasing lipid peroxidation by-products (thiobarbituric reactive substances, TBARS) and decreasing total thiols and total antioxidant power of the saliva. Concurrent therapy of rats by theophylline (25 mg/kg) and sildenafil (5 mg/kg) prevented cadmium-induced oxidative stress in saliva. Theophylline and sildenafil inhibited cadmium-induced increase in lipid peroxidation and decrease in total thiols and antioxidant power. It is concluded that cadmium administration results in oxidative stress in rat submandibular saliva, which can be protected by concurrent administration of specific cyclic nucleotide phosphodiesterase inhibitors. 相似文献
75.
Toshihiro Aoki Ikumi Hyohdoh Noriyuki Furuichi Sawako Ozawa Fumio Watanabe Masayuki Matsushita Masahiro Sakaitani Kazutomo Ori Kenji Takanashi Naoki Harada Yasushi Tomii Mitsuyasu Tabo Kiyoshi Yoshinari Yuko Aoki Nobuo Shimma Hitoshi Iikura 《Bioorganic & medicinal chemistry letters》2013,23(23):6223-6227
Introducing a sulfamide moiety to our coumarin derivatives afforded enhanced Raf/MEK inhibitory activity concomitantly with an acceptable PK profile. Novel sulfamide 17 showed potent HCT116 cell growth inhibition (IC50 = 8 nM) and good PK profile (bioavailability of 51% in mouse), resulting in high in vivo antitumor efficacy in the HCT116 xenograft (ED50 = 4.8 mg/kg). We confirmed the sulfamide moiety showed no negative impact on tests run on the compound to evaluate DMPK (PK profiles in three animal species, CYP inhibition and CYP induction) and the safety profile (hERG and AMES tests). Sulfamide 17 had favorable properties that warranted further preclinical assessment 相似文献
76.
从普通栽培型番茄品种‘桃太郎’、野生醋栗番茄和潘那利番茄的幼苗中采用RT-PCR方法,扩增出转化酶抑制子基因cDNA序列的部分片段。经测序表明:不同基因型番茄的转化酶抑制子基因同源性高达97.97%以上。采用半定量RT-PCR方法对‘桃太郎’苗期根、茎、叶和花后功能叶、花期子房以及果实不同发育阶段不同部位的表达进行检测,结果表明:INH在根中表达较弱,茎中有强烈表达,从幼叶到衰老叶表达逐渐减弱;同一时期INH在果肉中表达相对较强,维管束次之,胶质胎座相对较弱;花期子房中INH的表达逐渐增强,花后3d左右达到最大,花后5~8d表达量迅速下降。 相似文献
77.
Tadao Hashimoto Yukuo Yoshida Kunio Tagawa 《Journal of bioenergetics and biomembranes》1990,22(1):27-38
An intrinsic ATPase inhibitor inhibits the ATP-hydrolyzing activity of mitochondrial F1F0-ATPase and is released from its binding site on the enzyme upon energization of mitochondrial membranes to allow phosphorylation of ADP. The mitochondrial activity to synthesize ATP is not influenced by the absence of the inhibitor protein. The enzyme activity to hydrolyze ATP is induced by dissipation of the membrane potential in the absence of the inhibitor. Thus, the inhibitor is not responsible for oxidative phosphorylation, but acts only to inhibit ATP hydrolysis by F1F0-ATPase upon deenergization of mitochondrial membranes. The inhibitor protein forms a regulatory complex with two stabilizing factors, 9K and 15K proteins, which facilitate the binding of the inhibitor to F1F0-ATPase and stabilize the resultant inactivated enzyme. The 9K protein, having a sequence very similar to the inhibitor, binds directly to F1 in a manner similar to the inhibitor. The 15K protein binds to the F0 part and holds the inhibitor and the 9K protein on F1F0-ATPase even when one of them is detached from the F1 part. 相似文献
78.
79.
Sultan Ullah Yujin Park Muhammad Ikram Sanggwon Lee Chaeun Park Dongwan Kang Jungho Yang Jinia Akter Sik Yoon Pusoon Chun Hyung Ryong Moon 《Bioorganic & medicinal chemistry》2018,26(21):5672-5681
Pigmentation disorders are attributed to excessive melanin which can be produced by tyrosinase. Therefore, tyrosinase is supposed to be a vital target for the treatment of disorders associated with overpigmentation. Based on our previous findings that an (E)-β-phenyl-α,β-unsaturated carbonyl scaffold can play a key role in the inhibition of tyrosinase activity, and the fact that cinnamic acid is a safe natural substance with a scaffolded structure, it was speculated that appropriate cinnamic acid derivatives may exhibit potent tyrosinase inhibitory activity. Thus, ten cinnamamides were designed, and synthesized by using a Horner-Emmons olefination as the key step. Cinnamamides 4 (93.72% inhibition), 9 (78.97% inhibition), and 10 (59.09% inhibition) with either a 2,4-dihydroxyphenyl, or 4-hydroxy-3-methoxyphenyl substituent showed much higher mushroom tyrosinase inhibition at 25?µM than kojic acid (18.81% inhibition), used as a positive control. Especially, the two cinnamamides 4 and 9 having a 2,4-dihydroxyphenyl group showed the strongest inhibition. Docking simulation with tyrosinase revealed that these three cinnamamides, 4, 9, and 10, bind to the active site of tyrosinase more strongly than kojic acid. Cell-based experiments carried out using B16F10 murine skin melanoma cells demonstrated that all three cinnamamides effectively inhibited cellular tyrosinase activity and melanin production in the cells without cytotoxicity. There was a close correlation between cellular tyrosinase activity and melanin content, indicating that the inhibitory effect of the three cinnamamides on melanin production is mainly attributed to their capability for cellular tyrosinase inhibition. These results imply that cinnamamides having the (E)-β-phenyl-α,β-unsaturated carbonyl scaffolds are promising candidates for skin-lighting agents. 相似文献
80.
Boggiano C Jiang S Lu H Zhao Q Liu S Binley J Blondelle SE 《Biochemical and biophysical research communications》2006,347(4):909-915
Entry of human immunodeficiency virus type 1 (HIV-1) virion into host cells involves three major steps, each being a potential target for the development of entry inhibitors: gp120 binding to CD4, gp120-CD4 complex interacting with a coreceptor, and gp41 refolding to form a six-helix bundle. Using a D-amino acid decapeptide combinatorial library, we identified peptide dC13 as having potent HIV-1 fusion inhibitory activity, and effectively inhibiting infection by several laboratory-adapted and primary HIV-1 strains. While dC13 did not block binding of gp120 to CD4, nor disrupt the gp41 six-helix bundle formation, it effectively blocked the binding of an anti-CXCR4 monoclonal antibody and chemokine SDF-1alpha to CXCR4-expressing cells. However, because R5-using primary viruses were also neutralized, the antiviral activity of dC13 implies additional mode(s) of action. These results suggest that dC13 is a useful HIV-1 coreceptor antagonist for CXCR4 and, due to its biostability and simplicity, may be of value for developing a new class of HIV-1 entry inhibitors. 相似文献