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1.
Donald E. Rivett Dean Hewish Alan Kirkpatrick Jerome Werkmeister 《Journal of Protein Chemistry》1999,18(3):291-295
Nine fatty acid–peptide hybrid molecules were constructed using the general formula CH3(CH2)
n
CO-Phe Asp Cys-amide and tested for their ability to inhibit cell lysis induced by the membrane-active peptide melittin. All of these molecules, where n = 4–14, inhibited the action of melittin to some extent, but the longer carbon chains were most effective. Several potential inhibitors were also constructed with conservative substitutions in the peptide portion of the molecule. All were effective to varying degrees. We concluded that in the hexapeptide inhibitor published by Blondelle et al. (1993), the role of the first three residues is only to provide hydrophobic interaction with the melittin and has no particular amino acid sequence specificity. Some of these inhibitors were found to inhibit the lytic activity of a melittin analogue which had only superficial sequence similarity to melittin and also a truncated form of melittin, indicating the generality of the action of the inhibitors.Deceased 5/4/98 相似文献
2.
3.
Silvia Pastorekova Daniela Vullo Angela Casini Andrea Scozzafava Jaromir Pastorek Isao Nishimori 《Journal of enzyme inhibition and medicinal chemistry》2013,28(3):211-217
The tumor-associated transmembrane carbonic anhydrase (CA, EC 4.2.1.1) isozymes IX (CA IX) and XII (CA XII) are involved in acidification of hypoxic tumors, a process correlated with poor prognosis and clinical outcome of patients harboring such tumors. This process may be reversed by inhibiting these enzymes with potent sulfonamide/sulfamate inhibitors. A series of such aromatic/heterocyclic sulfonamides incorporating 2,3,5,6-tetrafluorobenzoyl-, 2,3,5,6-tetrafluoro- phenylsulfonyl- and pentafluorophenylureido moieties has been investigated for its interaction with the catalytic domain of the human isozymes hCA IX and hCA XII. Some of these compounds showed excellent inhibitory properties against both isozymes IX and XII, with several subnanomolar inhibitors detected for the first time. These sulfonamides may constitute valuable candidates for the development of novel antitumor therapies based on the inhibition of such tumor-associated CA isozymes. 相似文献
4.
Mr Gaston H. M. Vondenhoff Arthur Van Aerschot 《Nucleosides, nucleotides & nucleic acids》2013,32(7-8):465-474
The natural compound Microcin C (McC) is a Trojan horse inhibitor of aspartyl tRNA synthetases endowed with strong antibacterial properties, in which a heptapeptide moiety is responsible for active transport of the inhibitory metabolite part into the bacterial cell. The intracellularly formed aspartyl AMP analogue carries a chemically more stable phosphoramidate linkage, in comparison to the labile aspartyl-adenylate, and in addition is esterified with a 3-aminopropyl moiety. Therefore, this compound can target aspartyl-tRNA synthetase. The biochemical production and secretion of McC, and the possibilities to develop new classes of antibiotics using the McC Trojan horse concept in combination with sulfamoylated adenosine analogues will be discussed briefly. 相似文献
5.
《Biomarkers》2013,18(2):186-191
Context: Usefulness of circulating Chromogranin A (CgA) for the diagnosis of neuroendocrine tumors (NEN) is controversial. The aim of the present study was to assess the actual role of this marker as diagnostic tool. Methods: Serum blood samples were obtained from 42 subjects affected with NEN, 120 subjects affected with non-endocrine neoplasias (non-NEN) and 100 non-neoplastic subjects affected with benign nodular goitre (NNG). Determination of CgA was performed by means of immunoradiometric assay. Results: The CgA levels among NEN-patients were not significantly different from NNG and non-NEN subjects. The Receiver operating characteristic (ROC) curves analysis failed to identify a feasible cut-off value for the differential diagnosis between NEN and the other conditions. Conclusion: Serum CgA is not helpful for the first-line diagnosis of NEN. 相似文献
6.
Tudor H. Thomas 《Plant Growth Regulation》1989,8(3):255-261
The temperature-dependent, primary dormancy of cv. Florida 683 celery seeds in darkness was partially broken by a 30 min light exposure on the third day of incubation at 20–22°C, resulting in c 50 percent germination after 20 days. This light stimulation was negated by including different inhibitors of gibberellin biosynthesis in the incubation medium. Subsequent addition of a solution of the gibberellins A4 and A7 or of the gibberellin-active compound (1-3-chlorophthalimido)-cyclohexane carboxamide (AC94,377) overcame the inhibitory effects on germination of these GA-biosynthesis inhibitors. It is suggested that light stimulates the biosynthesis of gibberellins which are essential for dormancy-break in celery seeds and that this biosynthesis is either directly or indirectly controlled through phytochrome.Abbreviations AC94,377
1-(3-chlorophthalimido)-cyclohexane carboxamide; ancymidol, -cyclopropyl--(4-methoxyphenyl)-5-pyrimidinemethanol
- AMO1618
N,N,N-2-tetramethyl-5-(1-methyl ethyl)-4-(1-piperidinylcarbonyl)oxy-benzenaminium chloride
- BTS44584
S-2,5-dimethyl-4-pentamethylenecarbamoyloxyphenyl-SS-dimethyl sulphonium
- P
toluenesulphonate; chlormequat chloride, 2-chloroethyltrimethylammonium chloride; daminozide
- N
dimethylaminoscuccinamic acid; paclobutrazol, (2RS, 3RS)-1-(4-chlorophenyl)-4,4-dimethyl-2-(1H-1,2,4-triazol-1-yl pentan-3-ol) 相似文献
7.
J. E. Baker 《Entomologia Experimentalis et Applicata》1988,46(1):47-54
Rank transformation of specific activity values of -amylase across four strains of Sitophilus oryzae (L.) and four strains of S. zeamais Motschulsky indicates that levels of these predominant enzymes are highest in adults feeding on hulled barley or long-grain brown rice. Intermediate activity levels are found in weevils feeding on yellow corn (maize) and lowest levels are found in wheat-fed weevils. Although extracts prepared from barley contain inhibitory activity against two purified isoamylases from S. oryzae, levels of the naturally-occurring -amylase inhibitors against these two enzymes are about 2.2-fold and 6.1-fold, respectively, more concentrated in wheat. Ingestion of these amylase inhibitors and formation of an inactive enzyme:inhibitor complex with previously secreted amylase may account for the lower activity of amylase in weevils of both species feeding on wheat. Amylase levels across all strains feeding on a given diet are about 2-fold higher in S. oryzae than in S. zeamais. Significant differences in activity levels were also found between strains in both species. Since -amylase is a predominant digestive hydrolase in these species, the degree to which cereal diets affect amylase levels may indicate their suitability as potential hosts.
Résumé La transformation de rang des valeur d'activité spécifique de l'-amylase de 4 souches de S. oryzae et de 4 souches de S. zeamais montre que les niveaux les plus élevés de ces enzymes prédominantes s'observent chez les adultes nourris d'orge mondé ou de riz brun á grains longs. Des niveaux intermédiaires d'activité ont été obtenus chez les insectes élevés sur maïs jaune, et les niveaux les plus faibles chez ceux élevés sur blé. Bien que les extraits préparés à partir d'orge présentent une activité inhibitrice de deux isoamylases purifiées de S. oryzae, les niveaux des inhibiteurs naturels -amylase de ces deux enzymes sont environ respectivement 2,2 et 6,1 fois plus concentrés dans le blé. L'ingestion de ces inhibiteurs d'amylase et la formation d'un complexe enzyme inactive/inhibiteur avec l'amylase secrétée antérieurement, peut rendre compte de la plus faible activité de l'amylase chez les charançons consommant du blé. Le niveau d'amylase de S. oryzae est 2 fois plus élevé que celui de S. zeamais pour toutes les souches élevées sur un régime donné. Des niveaux d'activité significativement différents ont été trouvés suivant les souches pour chacune des deux espèces. Puisque l'amylase est la principale hydrolase digestive de ces espèces, l'intensité de la modification des teneurs en amylase par la consommation de céréales peut indiquer leur adéquation comme hôtes potentiels.相似文献
8.
Summary To examine the effects exerted on the microtubule (MT) cytoskeleton by dinitrophenol/deoxyglucose (DNP/DOG) and nocodazole, live PtK1 cells were treated with the drugs and then fixed and examined by immunofluorescence staining and electronmicroscopy. DNP/DOG had little effect on interphase MTs. In mitotic cells, kinetochore and some astral fibers were clearly shortened in metaphase figures by DNP/DOG. Nocodazole rapidly broke down spindle MTs (except those in the midbody), while interphase cells showed considerable variation in the susceptibility of their MTs. Nocodazole had little effect on MTs in energy-depleted (DNP/DOG-treated) cells. When cytoplasmic MTs had all been broken down by prolonged nocodazole treatment and the cells then released from the nocodazole block into DNP/DOG, some MT reassembly occurred in the ATP-depleted state. MTs in permeabilized, extracted cells were also examined with antitubulin staining; the well-preserved interphase and mitotic arrays of MTs showed no susceptibility to nocodazole. In contrast, MTs suffered considerable breakdown by ATP, GTP and ATPS; AMPPNP had little effect. This susceptibility of extracted MT cytoskeleton to nucleotide phosphates was highly variable; some interphase cells lost all MTs, most were severely affected, but some retained extensive MT networks; mitotic spindles were diminished but structurally coherent and more stable than most interphase MT arrays.We suggest that: 1. in the living cell, ATP or nucleotide triphosphates (NTPs) are necessary for normal and nocodazole-induced MT disassembly; 2. the NTP requirement may be for phosphorylation; 3. shortening of kinetochore fibers may be modulated by compression and require ATP; 4. many of these results cannot be accomodated by the dynamic equilibrium theory of MT assembly/disassembly; 5. the use and role of ATP on isolated spindles may have to be reevaluated due to the effects ATP has on the spindle cytoskeleton of permeabilized cells. 相似文献
9.
M Krieger 《Analytical biochemistry》1983,135(2):383-391
Pores formed in the membranes of animal cells by complexes of sterols and the polyene antibiotic amphotericin B can efficiently kill the cells. Thus, in the absence of exogenous sources of cholesterol, inhibitors of enzymes in the cholesterol biosynthetic pathway render cells resistant to amphotericin B. Preincubation of Chinese hamster ovary cells with compactin or 25-hydroxycholesterol, inhibitors of the synthesis of the key intermediate mevalonate, protected cells from amphotericin B killing and this protection was reversed by the addition of exogenous mevalonate. The ability of compactin to confer amphotericin B resistance on normal cells was abolished when cells were provided exogenous cholesterol by the receptor-mediated endocytosis of low density lipoprotein. Low density lipoprotein receptor-defective Chinese hamster ovary cells were not subject to this low density lipoprotein-dependent amphotericin B killing. Exogenous mevalonate did not prevent 4,4,10 beta-trimethyl-trans-decal-3 beta-ol, an inhibitor of mevalonate conversion to sterols, from protecting cells from amphotericin B. A simple two-step protocol in which cells are preincubated (15-24 h) with potential inhibitors and then treated (3-6 h) with amphotericin B was devised to provide a sensitive method for detecting direct (e.g., competitive) and regulatory inhibitors of cholesterol biosynthesis. This protocol may prove useful in detecting potential antihypercholesterolemia drugs and is currently being used to isolate mutants in receptor-mediated endocytosis. 相似文献
10.
The secretory nature of the excretory gland cells of Strephanurus dentatus. 3. Proteinase inhibitors 总被引:2,自引:0,他引:2
A proteinase inhibitor(s) was found in extracts of the excretory gland cells, intestines, esophagi, reproductive organs, and body walls from Stephanurus dentatus adults. The specific activity of the inhibitor(s) in the excretory gland cell extract was 45–175 times greater than in the other tissues. It is heat stable at pH 5.0 and inhibits the esterolytic activity of trypsin and chymotrypsin using p-toluenesulfonyl-l-arginine methyl ester hydrochloride (TAME) and benzoyl-l-tyrosine ethyl ester (BTEE) as the substrates, respectively, and also the proteolytic activity of both chymotrypsin and trypsin using casein as the substrate. S. dentatus adults maintained in NCTC 109 medium, secreted a trypsin inhibitor. 相似文献