全文获取类型
收费全文 | 7230篇 |
免费 | 349篇 |
国内免费 | 343篇 |
出版年
2024年 | 8篇 |
2023年 | 83篇 |
2022年 | 159篇 |
2021年 | 184篇 |
2020年 | 245篇 |
2019年 | 346篇 |
2018年 | 339篇 |
2017年 | 233篇 |
2016年 | 236篇 |
2015年 | 188篇 |
2014年 | 449篇 |
2013年 | 727篇 |
2012年 | 223篇 |
2011年 | 424篇 |
2010年 | 243篇 |
2009年 | 307篇 |
2008年 | 315篇 |
2007年 | 342篇 |
2006年 | 288篇 |
2005年 | 288篇 |
2004年 | 269篇 |
2003年 | 241篇 |
2002年 | 207篇 |
2001年 | 135篇 |
2000年 | 101篇 |
1999年 | 105篇 |
1998年 | 95篇 |
1997年 | 117篇 |
1996年 | 120篇 |
1995年 | 90篇 |
1994年 | 67篇 |
1993年 | 79篇 |
1992年 | 68篇 |
1991年 | 56篇 |
1990年 | 31篇 |
1989年 | 44篇 |
1988年 | 31篇 |
1987年 | 37篇 |
1986年 | 33篇 |
1985年 | 36篇 |
1984年 | 73篇 |
1983年 | 45篇 |
1982年 | 52篇 |
1981年 | 33篇 |
1980年 | 31篇 |
1979年 | 32篇 |
1978年 | 11篇 |
1977年 | 18篇 |
1976年 | 13篇 |
1974年 | 14篇 |
排序方式: 共有7922条查询结果,搜索用时 375 毫秒
61.
Bromo[1-14C]acetyl-CoA has been prepared from CoASH and the N-hydroxysuccinimide ester of bromo[1-14C]acetic acid, and unlabeled bromoacetyl-CoA by reaction of CoASH with bromoacetyl bromide. The products were purified by high-pressure liquid chromatography. Purified bromoacetyl-CoA was characterized, and found to be a potent alkylating agent with a substantial stability in aqueous solution: it decomposed at 30 degrees C and pH 6.6 and 8.0 with halftimes of 3.3 and 2.5 h, respectively. The major breakdown products were CoASH and CoAS X CO X CH2 X SCoA. Bromo[1-14C]acetyl-CoA has been used to affinity label the acetyl-CoA binding site of 3-hydroxy-3-methylglutaryl-CoA synthase from ox liver. It was found to irreversibly inhibit the enzyme activity and bind covalently with a stoichiometry for complete inhibition of about 0.8 mol/mol enzyme dimer. 相似文献
62.
The different isomers of the dipeptide beta-N-gamma-glutamyl diaminopropionate inhibit L-glutamate-1-carboxylyase (GAD, EC-4.1.1.15) activity in mouse brain homogenates. The L-D isomer is the most effective as an inhibitor, while the D-D isomer is least inhibitory. The different isomers are neurotoxic to mice and the chick, the L-D isomer being the most toxic. The neurotoxicity of the isomers in mice was also associated with a significant lowering in GAD activity in the brains of convulsing mice. 相似文献
63.
A neutral growth inhibitor, isolated from methanolic extracts of sunflower seedlings, was characterized by spectral data as caprolactam. Light-grown se 相似文献
64.
Judith M. Clarkson David L. Mitchell 《Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression》1983,740(4):355-361
The effect on DNA repair of several inhibitors of DNA synthesis has been investigated in CHO cells. Three assays were employed following ultraviolet irradiation of G1 cells: unscheduled DNA synthesis, removal of antibody binding sites and alkaline elution. Cytosine arabinoside and aphidicolin were found to reduce unscheduled DNA synthesis in a dose-dependent manner without affecting the removal of antibody-binding sites. Strand rejoining was also inhibited. These results are consistent with the hypothesis that inhibition is due to premature chain termination during repair synthesis some time after excision of the lesion. Conversely, inhibition of unscheduled DNA synthesis by novobiocin is paralleled by inhibition of excision of the lesion. However, no inhibition of incision was apparent. Since nalidixic acid, an inhibitor of topoisomerase II, did not inhibit excision, it is unlikely that the primary site of action of novobiocin is this topoisomerase. The possibility that a second topoisomerase and/or a polymerase are affected is discussed in the light of previously published data. 相似文献
65.
Makoto Suematsu Shigenari Houzawa Soichiro Miura Hiroshi Nagata Tetsuji Kitahora Tetsuo Morishita Chikara Oshio Masaharu Tsuchiya 《Luminescence》1989,4(1):531-534
Reaction difference of oxyradical generation and luminol-dependent photoemission of zymosan- and phorbol ester-treated neutrophils were investigated using a conventional photomultiplier and ultrasensitive photonic imaging technique. Zymosan-treated cells released a concentrated photonic burst corresponding to the cellular distribution. In contrast, phorbol ester-treated cells produced a negligible level of photoemission, and the additional application of Ca2+ ionophore enhanced the photonic burst, which was gradually spread out into extracellular space. Serine protease inhibitors did not attenuate PMA-induced chemiluminescence but did attenuate zymosan-induced chemiluminescence. This suggests the involvement of serine protease in the respiratory burst of phagocytizing neutrophils. 相似文献
66.
Conformational fluctuations in a globular protein, bovine pancreatic trypsin inhibitor, in the time range between picoseconds and nanoseconds are studied by a Monte Carlo simulation method. Multiple energy minima are derived from sampled conformations by minimizing their energy. They are distributed in clusters in the conformational space. A hierarchical structure is observed in the simulated dynamics. In the time range between 10(-14) and 10(-10) seconds dynamics is well represented by a superposition of vibrational motions within an energy well with transitions among minima within each cluster. Transitions among clusters take place in the time range of nanoseconds or longer. 相似文献
67.
Refinement of distance geometry (DG) structures of EETI-II (Heitz et al.: Biochemistry 28:2392-2398, 1989), a member of the squash family trypsin inhibitor, have been carried out by restrained molecular dynamics (RMD) in water. The resulting models show better side chain apolar/polar surface ratio and estimated solvation free energy than structures refined "in vacuo." The consistent lower values of residual NMR constraint violations, apolar/polar surface ratio, and solvation free energy for one of these refined structures allowed prediction of the 3D folding and disulfide connectivity of EETI-II. Except for the few first residues for which no NMR constraints were available, this computer model fully agreed with X-ray structures of CMTI-I (Bode et al.: FEBS Lett. 242:285-292, 1989) and EETI-II complexed with trypsin that appeared after the RMD simulation was completed. Restrained molecular dynamics in water is thus proved to be highly valuable for refinement of DG structures. Also, the successful use of apolar/polar surface ratio and of solvation free energy reinforce the analysis of Novotny et al. (Proteins 4:19-30, 1988) and shows that these criteria are useful indicators of correct versus misfolded models. 相似文献
68.
Endogenous Benzodiazepine Receptor Ligands in Human and Animal Hepatic Encephalopathy 总被引:6,自引:1,他引:5
Marjut Olasmaa Jeffrey D. Rothstein Alessandro Guidotti Richard J. Weber† Steven M. Paul‡ Sydney Spector§ Maria L. Zeneroli Mario Baraldi Erminio Costa 《Journal of neurochemistry》1990,55(6):2015-2023
The role of endogenous benzodiazepine receptor ligands in the pathogenesis of hepatic encephalopathy was studied in humans and in rat models of hepatic encephalopathy. Endogenous benzodiazepine ligands were extracted from rat brain and human CSF by acid treatment and purification by HPLC. Detection and partial characterization of these endogenous benzodiazepine ligands were carried out using both radioreceptor binding assays and radioimmunoassays with anti-benzodiazepine antibodies. Four different benzodiazepine receptor ligands were identified in human and rat tissue, two of which may be diazepam and desmethyldiazepam, based on elution profiles and anti-benzo-diazepine antibody reactivity. Human CSF and serum from patients with hepatic encephalopathy contained approximately 10 times more endogenous benzodiazepine receptor ligand than CSF from controls or nonencephalopathic patients with liver disease. The levels of brain benzodiazepine receptor ligand compounds were also increased approximately 10-fold in rats suffering from fulminant hepatic failure, but not in rats with portacaval shunts, a model of chronic hepatic disease. The increased concentrations of these substances could be behaviorally significant and may contribute to the pathogenesis of hepatic encephalopathy. 相似文献
69.
E. Slobodyansky A. Guidotti C. Wambebe A. Berkovich E. Costa 《Journal of neurochemistry》1989,53(4):1276-1284
This report describes the purification and characterization from rat brain of triakontatetraneuropeptide (TTN, DBI 17-50), a major biologically active processing product of diazepam binding inhibitor (DBI). Brain TTN was purified by immunoaffinity chromatography with polyclonal octadecaneuropeptide, DBI 33-50) antibodies coupled to CNBr-Sepharose 4B followed by two reverse-phase HPLC steps. The amino acid sequence of the purified peptide is: Thr-Gln-Pro-Thr-Asp-Glu-Glu-Met-Leu-Phe-Ile-Tyr-Ser-His-Phe-Lys-Gln-Ala-Thr-Val - Gly-Asp-Val-Asn-Thr-Asp-Arg-Pro-Gly-Leu-Leu-Asp-Leu-Lys. Synthetic TTN injected intracerebroventricularly into rats induces a proconflict activity (IC50 0.8 nmol/rat) that is prevented by the specific "peripheral" benzodiazepine (BZ) receptor antagonist isoquinoline carboxamide, PK 11195, but not by the "central" BZ receptor antagonist imidazobenzodiazepine, flumazenil. TTN displaces [3H]Ro 5-4864 from synaptic membranes of olfactory bulb with a Ki of approximately 5 microM. TTN also enhances picrotoxinin inhibition of gamma-aminobutyric acid (GABA)-stimulated [3H]flunitrazepam binding. These data suggest that TTN, a natural DBI processing product acting at "Ro 5-4864 preferring" BZ binding site subtypes, might function as a putative neuromodulator of specific GABAA receptor-mediated effects. 相似文献
70.
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