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41.
前列腺癌是中国发病率增长最快的男性肿瘤,抗雄激素治疗耐药是导致前列腺癌患者预后差的主要原因。因此,解决耐药性难题是前列腺癌转化研究的关键问题。哺乳动物细胞利用泛素-蛋白酶体系统实现蛋白质的靶向降解。因此,前列腺癌中关键的癌基因如雄激素受体(AR)的上游泛素化调控因子(如去泛素化酶)是潜在的治疗靶点。然而,这些酶具有较广的底物谱系,存在脱靶的可能性。近来,基于泛素-蛋白酶体系统开发的蛋白质降解靶向嵌合体(proteolysis-targeting chimeras,PROTAC)技术是最具前景和革命性的新型抗癌药物研发技术,能够利用特定E3泛素连接酶对靶蛋白进行降解而不影响其他底物。与传统小分子抑制剂相比,PROTAC分子在克服耐药性以及针对不可成药的靶点方面拥有巨大优势。目前,针对AR的PROTAC降解剂已在II期临床取得了成功,靶向蛋白质泛素化及降解途径的新技术将有望为前列腺癌的临床治疗带来新的突破。 相似文献
42.
43.
周荣华 《中国科学:生命科学英文版》1997,40(6):657-664
Using genomicin-situ hybridization (GISH) technique, 7 translocation-addition lines, 6 translocation and translocation-addition lines, 2 ditelosomic
addition lines and 1 translocation line were identified fromTriticum aestivum L. -Psathyrostachys juncea (Fisch.) Nevski intergeneric hybrids, of which translocation-addition and translocation and translocation-addition lines
were not found in other reports. No substitutions and disornic additions were detected in the, hybrids and breakages occurred
in allP. juncea chromosomes studied. Results have shown that the improved GISH technique is a rapid and economical method for use in this
field. 相似文献
44.
Spontaneous activity of neighboring auditory cortical neurons was derived by glass microelectrodes in chronic experiments on unanesthetized, unimmobilized cats, and the spike trains were subsequently analyzed by computer. Altogether 20 pairs of neurons were tested. The commonest type of interaction (50%) was found to be a common excitatory source, conjectured to be from specific auditory afferents. Interaction of the "common inhibitory source" (5%) and also complex forms of interaction were found. Interaction was absent in only 10% of cases. No direct inhibitory influence of neighboring neurons on one another was observed. The possible causes of absence of a direct inhibitory action are discussed. The most likely cause is absence of marked spontaneous activity in inhibitory auditory cortical neurons.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 16, No. 2, pp. 161–167, March–April, 1984. 相似文献
45.
Sh M Kocharian 《Genetika》1977,13(7):1252-1259
Mutations of the resistance to 2,6-diaminopurine (apt), which affect adenine phosphoribosyltransferase, fail to permit the growth of Escherichia coli pur mutants (purine auxotrophs which cannot make inosine monophosphate de novo) on the medium with 2,6-diaminopurine (DAP) as the sole source of purines. Addition of a small amount of hypoxantine, but not guanine, stimulated the growth of mutants of pur apt and pur apt+ genotypes on the medium with DAP. The utilization of DAP as purine source in the presence of hypoxantine is blocked by mutations guaC (guanosine monophosphate reductase), add (adenosine deaminase) and pup (purine necleoside phosphorylase), suggesting that DAP are utilized via purine nucleoside phosphorylase and adenosine deaminase. The drm mutation (that increases the level of pentose-1-phosphate in the cell) does not activate the utilization of DAP. The results indicate that a step, that limits the utilization of DAP as the sole source of purines by pur mutants of E. coli, is the deamination of DAP nucleoside. 相似文献
46.
Using L-cells both sensitive and resistant to cytotoxic action of ethidium bromide (EB), a study was made of the intracellular level of cAMP, activities of adenylcyclase, phosphodiesterase and cAMP, liberated from cells into the surrounding medium. In EB resistant L-cells compared to EB sensitive ones, the higher level of cAMP with a decreased activity of adenylcyclase and an increased activity of the phosphodiesterase was shown to be associated with an impeded exit of cAMP from cells. It is suggested that the differences in cAMP levels in the EB sensitive and resistant cells are associated with the properties of cAMP-dependent protein kinases of these cells. 相似文献
47.
48.
I.A. Zakharova Ja.V. Salyn L.V. Tatjanenko Yu.Sh. Mashkovsky G. Ponticelli 《Journal of inorganic biochemistry》1981,15(1):89-92
The investigation of the inhibitory activity on the membrane bonded ATP-ase of the M(L)2X2 complexes [where M = Pd(II), Pt(II); L = isoxazole(isox), 3,5-dimethylisoxazole(3,5-diMeisox), 3-methyl,5-phenylisoxazole(3-Me,5-Phisox), 3,5-diphenylisoxazole-(3,5-diPhisox), and 4-amino-3,5-dimethylisoxazole(4-ADI); X = Cl, Br] is reported. These results show that the complexes with isox and its methyl and phenyl derivatives have a much stronger inhibitory effect than the corresponding free ligands; in the 4-ADI compounds this activity drops. The Pd(II) complexes have a greater effect than the Pt(II) derivatives. The interaction occurs with SH groups and probably also with other active centers of the enzyme. These conclusions have been correlated with the E.S.C.A. spectra. These measurements show that the electron density of the complexes on the central metal ion and Nring atom or Nring and N-hexocyclic atoms on passing from chloride to bromide derivatives changes slightly. 相似文献
49.
The lattice-model of Changeux, Thiery, Tung & Kittel (1966) was extended in order to examine the co-operative response of chemically excitable membrane and the exact mathematical correspondence to the Ising model was shown. In this model, two conformational states S and R with different affinities for the ligand are assumed to be accessible to each protomer, which is interacting with the nearest-neighbor protomers. The model is applicable to any kind of symmetrically interacting system consisting of oligomers and lattices and is an extension of previously proposed models of allosteric protein. It includes the model of Monod, Wyman, & Changeux (1965) and that of Koshland, Némethy & Filmer (1966) as the extreme cases of the oligomer. By assuming that a state-transition from S to R in a protomer is accompanied by a unit increase in conductance, the characteristics of dose-response curves of chemically excitable membrane are examined. The Hill's coefficient nH of dose-response curve, the measure of the co-operativity, is shown to be proportional to the square of the mean fluctuation of the state function, the fraction of protomers in R state. 相似文献
50.
The pancreatic epithelium of intact frog has been studied using morphometry, cytochemistry and electron microscopy. A low level of DNA synthesis was shown to be characteristic of pancreatic epithelium of frogs caught in winter. The B/A cell volume ratio is 3.68 +/- 0.16 and 2.55 +/- 0.36 in small and median pancreatic islets, resp. A-, B-, D-cells are found in pancreatic islets, and intermediate acinar A and acinar B cells in intact frog pancreas. 相似文献