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181.
Barnett YA Eger K Eriksson S Folkers G Hansen PE Hofbauer R Komitowsky D Milon A Munch-Petersen B;European Thymidine Kinase Study Group 《Biotechnology advances》1994,12(4):663-668
A precondition for the chemotherapeutic treatment of a variety of virally-induced human diseases and malignant conditions is a highly selective interaction of the drug molecule to be used with it's biological target. To ensure the development of novel, effective drugs, it is essential that the biological target is well characterised with regard to it's structure and activity. Such characterisation relies upon adequate amounts of pure target being available. One of the most important enzymatic importers for antimetabolites is the enzyme thymidine kinase. In this article an in vitro protein expression system is described which facilitates the production of milligram amounts of pure and biologically active thymidine kinase, from a number of important biological sources. Results have shown that the in vitro produced enzyme has the exact biochemical propeties of the in vivo enzyme. Thus the in vitro protein expression system is an ideal vechicle to facilitate an in depth investigation of the enzyme's biological properties. 相似文献
182.
Zhao Ying Hiromasa Tojo Takanori Komatsubara Manabu Nakagawa Masami Inada Sumio Kawata Yuji Matsuzawa Mitsuhiro Okamoto 《生物化学与生物物理学报:疾病的分子基础》1994,1226(2):201-205
Enzyme activity, protein contents, and mRNA contents of group II phospholipase A2 (PLA2) in hepatocellular carcinoma (HCC) surgically obtained from 8 patients were compared with those in either its neighboring liver tissues or control liver tissues. The PLA2 specific activity towards the mixed micelles of 1-palmitoyl-2-oleoyl-phosphatidylglycerol and cholate was significantly greater in the tumor tissues (6.62 ± 1.46 nmol/min/mg) than those in the surrounding liver tissues (1.33 ± 0.22 nmol/min/mg) and controls (0.43 ± 0.04 nmol/min/mg). The results of immunoblot analysis using a specific anti-human group II PLA2 antibody and of Northern blot analysis using a human group II PLA2 cDNA as a probe demonstrated that group II PLA2 was responsible for the increased enzyme activity. The contents of immunoreactive group II PLA2 in the tumor tissues (8.81 ± 1.24 ng/mg) were significantly higher than those in the surrounding liver tissues (1.77 ± 0.27 ng/mg); those in the control tissues were below the analytical range of the method used. The group II PLA2 mRNA was also significantly increased in the tumor tissues, compared with that in the surrounding liver tissues, whereas it was not detectable in th controls. This indicates that group II PLA2 in HCC is induced at the pretranslational level. 相似文献
183.
Alwin Krmer Jan Pudil Heinz Frank Franz Oesch Handruedi Glatt 《Mutation research》1993,290(2):165-174
Trans-stilbene oxide, trans-β-methylstyrene, 7,8-oxide, trans-β-ethylstyrene, 7,8-oxide, trans-β-propylstyrene 7,8-oxide and 4-fluorochalcone oxide were investigated for genotoxic activity in bacterial and mammalian cells, in the absence of external xenobiotic-metabolising systems. All compounds strongly enhanced the frequency of sister-chromatid exchanges (SCE) in cultured human lymphocytes. None of them was mutagenic in Salmonella typhimurium (reversion of the his− strains TA98, TA100 and TA104). The limit of detection was 1/20,000 to 1/106 of the activity of the positive control, benzo[a]pyrene 4,5-oxide, depending on the compound and the bacterial strain. Trans-β-methylstyrene 7,8-oxide and 4-fluorochalcone oxide were additionally tested for induction of SCE and gene mutations in the same target cells, namely Chinese hamster V79 cells. Their influence on the level of SCE was similar to that observed in human lymphocytes, whilst gene mutations (at the hprt locus) were not induced. The four investigated styrene oxide derivatives are known to be excellent substrates for a mammalian enzyme, cytosolic epoxide hydrolase (cEH). 4-Fluorochalcone oxide is a potent selective inhibitor of this enzyme and is structurally similar to the investigated styrene oxide derivatives. These properties of the test compounds however cannot explain the observed discrepancies in the results, since the genetic end point (SCE versus gene mutations) was decisive, and SCE were induced in cEH-proficient human lymphocytes as well as in cEH-deficient V79 cells. 相似文献
184.
High-affinity folate binding in human prostate 总被引:1,自引:0,他引:1
Binding of3H-folate in Triton X-100 solubilized human prostate homogenate was of a high-affinity type and displayed apparent positive cooperativity typical of specific folate binding. Radioligand dissociation was slow at pH 7.4, but rapid at pH 3.5. Gel chromatography reveled two major folate binding proteins (Mr100 and 25kDa), but only one single band (Mr65–70 kDa) was detectable on SDS-PAGE and immunoblotting with rabbit-anti human milk folate binding protein. Concentration of folate binding protein in prostate homogenate expressed as maximum3H-folate binding was 1.10 nmol/g protein, and the cross-reactivity with rabbit-anti human milk folate binding protein serum was 15% as determined by an enzyme-linked immunosorbent assay (median values; n=6). 相似文献
185.
Christine Delporte Anne Van Praet Andre Herchuelz Jacques Winand Jean Christophe 《Peptides》1993,14(6):1111-1118
The effects of PACAPs on [Ca2+]i were compared to those of carbachol in human neuroblastoma NB-OK-1 cells. PACAP(1–27) and PACAP(1–38) increased [Ca2+]i in a biphasic manner: a transient rise and a secondary plateau. The transient phase reflected the mobilization of [Ca2+]i pool(s) via the inositol phosphate pathway. The modest sustained plateau required extracellular Ca2+. Carbachol also increased [Ca2+]i in a biphasic manner, but it mobilized intracellular Ca2+ pool(s) with a higher efficacy than PACAPs, then greatly increased Ca2+ entry, this being accompanied by a more marked and prolonged elevation of IP3 and IP4 than with PACAPs. It is likely that cAMP-mediated phosphorylations due to PACAPs facilitated desensitization at the PACAP receptor-phospholipase C level, so that there was less Ca2+ handling through PACAP receptors than with muscarinic M1 receptors. 相似文献
186.
ExistenceandFunctionsofNeurotensinHumanEarlyPlacentalVilliZHANGChong-li(张崇理);CHENGLi-ren(程丽仁),SHENWei-bin(沈卫斌);YINHong(殷红);HU... 相似文献
187.
In the present study, immunogold labeling of ultrathin sections of ejaculated sperm was used to obtain insight into the ultrastructural localization and presumable function of type II cAMP-dependent protein kinase in sperm motion. In the flagellum, a human-specific isoform of the RIIα subunit was located on the axonemal microtubule wall, whereas a different isoform of broader specificity was present in the cytoplasm at the periphery of the coarse fibers and fibrous sheath. This isoform was also found in the mitochondria. The human-specific RIIα subunit is likely linked to microtubules by a unique binding protein of Mr 72kD. These findings are in agreement with the concept of a concerted mechanism involving phosphorylation of both the axonemal microtubules and the fibrous structures for the regulation of mammalian sperm motion. © 1994 Wiley-Liss, Inc. 相似文献
188.
M. Maes F. De Meyer D. Peeters H. Meltzer C. Schotte S. Scharpe P. Cosyns 《International journal of biometeorology》1993,37(2):78-82
Recently, some investigators have established a seasonal pattern in normal human psychology, physiology and behaviour, and in the incidence of psychiatric psychopathology. In an attempt to elucidate the chronopsy and meteotropism in the latter, we have examined the chronograms of, and the biometeorological relationships to bed occupancy of the psychiatric ward of the Antwerp University Hospital during three consecutive calendar years (1987–1989). Weather data for the vicinity were provided by a local meteorological station and comprise mean atmospheric pressure, air temperature, relative humidity, wind speed and minutes of sunlight and precipitation/day. The number of psychiatric beds occupied during the study period exhibited a significant seasonal variation. Peaks in bed occupancy were observed in March and November, with lows in August. An important part of the variability in the number of beds occupied could be explained by the composite effects of weather variables of the preceding weeks. Our results suggest that short-term fluctuations in atmospheric activity may dictate some of the periodicities in psychiatric psychopathology. 相似文献
189.
190.
L. Pradier E. Heuillet J. P. Hubert M. Laville S. Le Guern A. Doble 《Journal of neurochemistry》1993,61(5):1850-1858
Abstract— In the human astrocytoma cell line U 373 MG, application of substance P (SP) leads to a transient increase in cytosolic calcium concentration and to a biphasic current response in voltage-clamped cells. Using these two functional assays we have characterized pharmacologically the SP response in U 373 MG cells. SP and [l -Pro9]SP displayed high potencies in both assays with EC50values of 2.5 ± 10?9M and 1 ± 10?9M on calcium responses and 110?9M and 510?9M on ion current responses, respectively. The high potency of SP and [l -Pro9]SP as well as the low potency of [Lys5,MeLeu9,N-Leu10]neurokinin A(4-10) and the inactivity of senktide demonstrate the NK1-type pharmacology of these responses. Furthermore, the NK1 antagonists (±)-CP 96,345, its chloro analogue, (±)-cis-3-(2-chlorobenzylamino)-2-benz-hydrylquinuclidine, and RP 67580 were potent antagonists of both SP responses. For the calcium mobilization induced by SP (1 (10?7M), the IC50 values for the three antagonists were 4 ± 10?10M, 4 ± 10?9M, and 9 ± 10?9M, respectively, whereas on the current response evoked by SP 10?8M), the IC50 values were 8 ± 10?9M, 2.4 ± 10?8M, and 1.2 10?7M, respectively. Despite differences in the absolute IC50 values obtained with both techniques, the relative potencies of the three antagonists correlate fairly well. The U 373 MG cell line provides a useful model system for studies of the pharmacology of the human NK1receptor and its transduction mechanisms at the level of second messengers and modulation of ion currents. 相似文献