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991.
Gallagher BM Fang FG Johannes CW Pesant M Tremblay MR Zhao H Akasaka K Li XY Liu J Littlefield BA 《Bioorganic & medicinal chemistry letters》2004,14(3):575-579
Analogues of the marine natural product (-)-laulimalide were prepared by total synthesis and evaluated in vitro for anticancer activity. 相似文献
992.
Li J DeMello KM Cheng H Sakya SM Bronk BS Rafka RJ Jaynes BH Ziegler CB Kilroy C Mann DW Nimz EL Lynch MP Haven ML Kolosko NL Minich ML Li C Dutra JK Rast B Crosson RM Morton BJ Kirk GW Callaghan KM Koss DA Shavnya A Lund LA Seibel SB Petras CF Silvia A 《Bioorganic & medicinal chemistry letters》2004,14(1):95-98
Structure-activity relationship (SAR) studies of 2-[3-di(and tri)fluoromethyl-5-arylpyrazol-1-yl]-5-methanesulfonylpyridine derivatives for canine COX enzymes are described. This led to the identification of 12a as a lead candidate for further progression. The in vitro and in vivo activity of 12a for the canine COX-2 enzyme as well as its in vivo efficacy and pharmacokinetic properties in dog are highlighted. 相似文献
993.
Heasley BH Jarosz R Carter KM Van SJ Lynch KR Macdonald TL 《Bioorganic & medicinal chemistry letters》2004,14(15):4069-4074
A recently reported dual LPA(1)/LPA(3) receptor antagonist (1) has been modified so as to modulate the basicity, sterics, and dipole moment of the 2-pyridyl moiety. Additionally, the implications of installing nonhydrolyzable phosphate head group isosteres with regard to antagonist potency and selectivity at LPA receptors is described. This study has resulted in the development of the first nonhydrolyzable and presumably phosphatase-resistant LPA(3)-selective antagonist reported to date. 相似文献
994.
Potentiation of cytotoxic drug activity in human tumour cell lines, by amine-substituted 2-arylbenzimidazole-4-carboxamide PARP-1 inhibitors 总被引:3,自引:0,他引:3
White AW Curtin NJ Eastman BW Golding BT Hostomsky Z Kyle S Li J Maegley KA Skalitzky DJ Webber SE Yu XH Griffin RJ 《Bioorganic & medicinal chemistry letters》2004,14(10):2433-2437
The synthesis and biological evaluation of a new series of amine-substituted 2-arylbenzimidazole-4-carboxamide inhibitors of the DNA-repair enzyme poly(ADP-ribose) polymerase-1 (PARP-1) is reported. The introduction of an amine substituent at the 2-aryl position is not detrimental to activity, with most inhibitors exhibiting K(i) values for PARP-1 inhibition in the low nanomolar range. Two compounds in this series were found to potentiate the cytotoxicity of the DNA-methylating agent temozolomide by 4-5-fold in a human colorectal cancer cell line. 相似文献
995.
Novobiocin was recently shown to inhibit Hsp90 through a previously unrecognized C-terminal ATP binding site. Although the N-terminal region of Hsp90 has been solved by X-ray crystallography, the C-terminal region has not. In an effort to elucidate the C-terminal binding site of Hsp90, four photolabile analogues of novobiocin were prepared. 相似文献
996.
Gray D Plusa B Piotrowska K Na J Tom B Glover DM Zernicka-Goetz M 《Current biology : CB》2004,14(5):397-405
Although mouse development is regulative, the cleavage pattern of the embryo is not random. The first cleavage tends to relate to the site of the previous meiosis. Sperm entry might provide a second cue, but evidence for and against this is indirect and has been debated. To resolve whether sperm entry position relates to the first cleavage, we have followed development from fertilization by time-lapse imaging. This directly showed cytokinesis passes close to the site of the previous meiosis and to both the sperm entry site and trajectory of the male pronucleus in a significant majority of eggs. We detected asymmetric distribution of Par6 protein in relation to the site of meiosis, but not sperm entry. Unexpectedly, we found the egg becomes flattened upon fertilization in an actin-mediated process. The sperm entry position tends to lie at one end of the short axis along which cleavage will pass. When we manipulated eggs to change their shape, this repositioned the cleavage plane such that eggs divided along their experimentally imposed short axis. Such manipulated eggs were able to develop to term, emphasizing the regulative nature of their development. 相似文献
997.
BACKGROUND: The meiotic cell cycle, the cell division cycle that leads to the generation of gametes, is unique in that a single DNA replication phase is followed by two chromosome segregation phases. During meiosis I, homologous chromosomes are segregated, and during meiosis II, as in mitosis, sister chromatids are partitioned. For homolog segregation to occur during meiosis I, physical linkages called chiasmata need to form between homologs, sister chromatid cohesion has to be lost in a stepwise manner, and sister kinetochores must attach to microtubules emanating from the same spindle pole (coorientation). RESULTS: Here we show that the meiosis-specific factor Spo13 functions in two key aspects of meiotic chromosome segregation. In cells lacking SPO13, cohesin, which is the protein complex that holds sister chromatids together, is not protected from removal around kinetochores during meiosis I but is instead lost along the entire length of the chromosomes. We furthermore find that Spo13 promotes sister kinetochore coorientation by maintaining the monopolin complex at kinetochores. In the absence of SPO13, Mam1 and Lrs4 disassociate from kinetochores prematurely during pro-metaphase I and metaphase I, resulting in a partial defect in sister kinetochore coorientation in spo13 Delta cells. CONCLUSIONS: Our results indicate that Spo13 has the ability to regulate both the stepwise loss of sister chromatid cohesion and kinetochore coorientation, two essential features of meiotic chromosome segregation. 相似文献
998.
999.
A common open representation of mass spectrometry data and its application to proteomics research 总被引:12,自引:0,他引:12
Pedrioli PG Eng JK Hubley R Vogelzang M Deutsch EW Raught B Pratt B Nilsson E Angeletti RH Apweiler R Cheung K Costello CE Hermjakob H Huang S Julian RK Kapp E McComb ME Oliver SG Omenn G Paton NW Simpson R Smith R Taylor CF Zhu W Aebersold R 《Nature biotechnology》2004,22(11):1459-1466
A broad range of mass spectrometers are used in mass spectrometry (MS)-based proteomics research. Each type of instrument possesses a unique design, data system and performance specifications, resulting in strengths and weaknesses for different types of experiments. Unfortunately, the native binary data formats produced by each type of mass spectrometer also differ and are usually proprietary. The diverse, nontransparent nature of the data structure complicates the integration of new instruments into preexisting infrastructure, impedes the analysis, exchange, comparison and publication of results from different experiments and laboratories, and prevents the bioinformatics community from accessing data sets required for software development. Here, we introduce the 'mzXML' format, an open, generic XML (extensible markup language) representation of MS data. We have also developed an accompanying suite of supporting programs. We expect that this format will facilitate data management, interpretation and dissemination in proteomics research. 相似文献
1000.
Speake BK Herbert JF Thompson MB 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2004,139(2):213-220
During gestation in the viviparous lizard Pseudemoia entrecasteauxii, the fetus obtains nutrients from two sources: uptake of yolk components from the retained egg (lecithotrophy) and transfer of nutrients from the maternal circulation via the placenta (placentotrophy). Although net placentotrophy in this species is indicated by the observation that the neonate contains 1.7 times more dry matter than the egg, the placental transfer of lipid has not been previously demonstrated. Lipid analysis was performed on newly ovulated eggs and on neonates. The weight of total lipid per neonate (8.2+/-0.5 mg) is significantly (P=0.049) greater than that in the egg (6.8+/-0.4 mg), indicating that the placenta must contribute some lipid to the fetus. On the assumption that 50% of the lipid delivered to the fetus from either source is oxidized for energy, it is calculated that the placenta accounts for 58.5% of the fetal lipid requirements, with the remaining 41.5% being derived from the egg. The fatty acid compositions of the triacylglycerol and phospholipid recovered in the neonatal tissue differ substantially from those of the egg. In particular, the proportions of 18:2n-6 and 18:3n-3 are far lower in the neonatal lipids compared with the egg lipids. On the other hand, the proportion of 22:6n-3 in the phospholipid of the neonate is six times higher than in the phospholipid of the egg. The absolute amount (mg) of 22:6n-3 recovered in the total lipid of the neonate is 3.8 times greater than the amount initially present in the egg. By comparison, the amount of total fatty acid in neonatal lipid is 1.2 times greater than the amount in the egg. Thus, there is a preferential use of 22:6n-3 for tissue phospholipid synthesis during development. We conclude that there is net transfer of fatty acids across the placenta to the fetus of P. entrecasteauxii and a high degree of selectivity in the use of the various fatty acids for fetal tissue lipid synthesis. 相似文献