全文获取类型
收费全文 | 8391篇 |
免费 | 698篇 |
国内免费 | 2篇 |
出版年
2023年 | 33篇 |
2021年 | 58篇 |
2020年 | 41篇 |
2019年 | 46篇 |
2018年 | 152篇 |
2017年 | 162篇 |
2016年 | 238篇 |
2015年 | 411篇 |
2014年 | 399篇 |
2013年 | 543篇 |
2012年 | 731篇 |
2011年 | 681篇 |
2010年 | 426篇 |
2009年 | 321篇 |
2008年 | 545篇 |
2007年 | 576篇 |
2006年 | 537篇 |
2005年 | 573篇 |
2004年 | 537篇 |
2003年 | 486篇 |
2002年 | 444篇 |
2001年 | 36篇 |
2000年 | 61篇 |
1999年 | 65篇 |
1998年 | 66篇 |
1997年 | 40篇 |
1996年 | 38篇 |
1995年 | 43篇 |
1994年 | 37篇 |
1993年 | 36篇 |
1992年 | 58篇 |
1991年 | 38篇 |
1990年 | 38篇 |
1989年 | 34篇 |
1988年 | 29篇 |
1987年 | 28篇 |
1986年 | 18篇 |
1985年 | 28篇 |
1984年 | 40篇 |
1983年 | 27篇 |
1982年 | 35篇 |
1981年 | 37篇 |
1980年 | 41篇 |
1979年 | 30篇 |
1978年 | 34篇 |
1977年 | 29篇 |
1976年 | 31篇 |
1975年 | 25篇 |
1974年 | 18篇 |
1973年 | 17篇 |
排序方式: 共有9091条查询结果,搜索用时 421 毫秒
71.
Sophie Stettler Nuchanard Chiannilkulchai Sylvie Hermann-Le Denmat Dominique Lalo François Lacroute André Sentenac Pierre Thuriaux 《Molecular genetics and genomics : MGG》1993,238(1-2):169-176
The pem locus, which is responsible for the stable maintenance of the low copy number plasmid R100, contains the pemK gene, whose product has been shown to be a growth inhibitor. Here, we attempted to isolate mutants which became tolerant to transient induction of the PemK protein. We obtained 20 mutants (here called pkt for PemK tolerance), of which 9 were temperature sensitive for growth. We analyzed the nine mutants genetically and found that they could be classified into three complementation groups, pktA, pktB and pktC, which corresponded to three genes, ileS, gltX and asnS, encoding isoleucyl-, glutamyl- and asparaginyl-tRNA synthetases, respectively. Since these aminoacyl-tRNA synthetase mutants did not produce the PemK protein upon induction at the restrictive temperature, these mutants could be isolated because they behaved as if they were tolerant to the PemK protein. The procedure is therefore useful for isolating temperature-sensitive mutants of aminoacyl-tRNA synthetases. 相似文献
72.
Initiatedlselected (ISH) and normal (NH) rat hepatocytes were used to study cytoskeleton modifications induced by three liver acting chemicals: 2-AAF, a liver complete carcinogen; PB, a liver tumor promoter; and 4-AAF, a noncarcinogen analogue of 2-AAF. Cytoskeleton alterations were visualized by disappearance of F-actin fibers and tubulin depolymerization. The three drugs induced actin fragmentation in normal hepatocytes; a net loss of actin protein was observed with PB. They also induced varied tubulin depolymerization. The principal difference between chemicals is that 2-AAF led to non-reversible effects, in comparison with PB and 4-AAF which induced reversible damages on cytoskeleton. By contrast to normal hepatocytes, the cytoskeleton of ISH obtained from rats subjected to the resistant hepatocyte protocol was much less susceptible to the effect of the three chemicals. Moreover, we observed a lack of LDH release in the culture medium and a very rapid inducibility of GST activity after exposure of ISH to drugs. The moderate effect of the three chemicals on actin and tubdin in ISH could thus be explained by the resistant metabolic profile of these cells.Abbreviations TPA
12-O-tetradecanoyl-phorbol-13-acetate
- PB
phenobarbital
- 2-AAF
2-acetylaminofluorene
- 4-AAF
4-acetylaminofluorene
- GSH
reduced glutathione
- GST
glutathione-S-transferase
- LDH
lactatedehydrogenase
- NH
normal hepatocytes
- ISH
initiated/selected hepatocytes
- BSA
bovine serum albumin 相似文献
73.
Marie-Dominique Rhoda-Hardy-Dessources René-Serge de Neef Guy Mérault Françoise Giraud 《生物化学与生物物理学报:疾病的分子基础》1993,1181(1):90-96
PtdIns and PtdInsP kinases from normal erythrocyte (AA) membranes and sickle cell anaemia erythrocyte (SS) membranes have been characterized. PtdIns kinase was studied in native membranes under conditions in which PtdInsP kinase and PtdInsP phosphatase do not express any activity. Kinetic analysis of the AA and SS PtdIns kinases indicate similar Km values for PtdIns and ATP but higher Vmax values for SS PtdIns kinase. PtdInsP kinase was partially purified from erythrocyte ghosts by NaCl extraction. The kinetic parameters of PtdInsP kinase determined under these conditions were similar in AA and SS NaCl extracts. These data suggest the presence of some effector of PtdIns kinase in SS cell membranes, resulting in a greater activity of the enzyme. This leads consequently, to increase the PtdInsP pool and to activate PtdInsP kinase, in agreement with our previous observations of a greater [32P]Pi incorporation in both polyphosphoinositides in SS cells relatively to AA cells. 相似文献
74.
Jérémy Gauthier Joana Meier Fabrice Legeai Melanie McClure Annabel Whibley Anthony Bretaudeau Hélène Boulain Hugues Parrinello Sam T. Mugford Richard Durbin Chenxi Zhou Shane McCarthy Christopher W. Wheat Florence Piron-Prunier Christelle Monsempes Marie-Christine François Paul Jay Camille Noûs Emma Persyn Emmanuelle Jacquin-Joly Camille Meslin Nicolas Montagné Claire Lemaitre Marianne Elias 《Molecular ecology resources》2023,23(4):872-885
The ithomiine butterflies (Nymphalidae: Danainae) represent the largest known radiation of Müllerian mimetic butterflies. They dominate by number the mimetic butterfly communities, which include species such as the iconic neotropical Heliconius genus. Recent studies on the ecology and genetics of speciation in Ithomiini have suggested that sexual pheromones, colour pattern and perhaps hostplant could drive reproductive isolation. However, no reference genome was available for Ithomiini, which has hindered further exploration on the genetic architecture of these candidate traits, and more generally on the genomic patterns of divergence. Here, we generated high-quality, chromosome-scale genome assemblies for two Melinaea species, M. marsaeus and M. menophilus, and a draft genome of the species Ithomia salapia. We obtained genomes with a size ranging from 396 to 503 Mb across the three species and scaffold N50 of 40.5 and 23.2 Mb for the two chromosome-scale assemblies. Using collinearity analyses we identified massive rearrangements between the two closely related Melinaea species. An annotation of transposable elements and gene content was performed, as well as a specialist annotation to target chemosensory genes, which is crucial for host plant detection and mate recognition in mimetic species. A comparative genomic approach revealed independent gene expansions in ithomiines and particularly in gustatory receptor genes. These first three genomes of ithomiine mimetic butterflies constitute a valuable addition and a welcome comparison to existing biological models such as Heliconius, and will enable further understanding of the mechanisms of adaptation in butterflies. 相似文献
75.
Rabbits immunized withBrucella suis within a period of one week formed antibodies in high titres. These antibodies were of a macroglobulin character only. Cells from the spleen and popliteal lymph nodes were cultivatedin vitro in protein-free medium, in which the only macromolecular substance was dextran or carbowax. Physico-chemical analysis of secretion products was not succesful, since under the given cultivation conditions the cells started to disintegrate from the outset and the medium contained nucleic acids as well as proteins. Some of these substances were present in particles of the size of different subcellular particles. After cultivation of spleen and lymph node cells, antibodies were detected by an agglutination test in media containing dextran and carbowax. When particles substantially larger than the antibody molecule were removed by ultracentrifugation, the agglutination antibody titre in the medium fell. 相似文献
76.
In commercial digested and purified horse diphtheria antitoxin, which is formed largely of the gamma globulin fragment with the sedimentation coefficient 5.3 S, the reactive disulphide bonds were destroyed by S-sulphonation. Gel filtration on Sephadex G-100 in 0.05 M formic acid with 6 M urea showed that the molecule of the S-sulphonated preparation dissociated into chains similar in character to the peptide chains of native horse antitoxins. Antibody activity was still partly maintained even after treatment with 6 M urea. On mixing the two types of chains isolated by gel filtration, antibody activity was recovered, the amount of antibody protein determined in the mixed fractions being greater than the sum of the amounts in the separate fractions. The neutralizing activity of the mixed fractions tested against toxinin vivo was also greater than the sum of the activity of the separate fractions. 相似文献
77.
Wolbachia are strictly endocellular, vertically transmitted bacteria associated with insects and crustaceans. This group of parasites modify their hosts' reproduction so as to increase their own fitness. This paper reviews the variability of these parasitic alterations and their consequences for host biology and populations. Wolbachia induce cytoplasmic incompatibility (a characteristic apparently specific to Wolbachia) in several insects and one isopod crustacean; parthenogenesis (thelytoky) in haplo-diploid insects; feminization in various isopods. The consequences of these phenomena on speciation, population dynamics and genetic polymorphism are discussed. The variability of the mechanisms of host sex determination is one important factor responsible for the diversity of Wolbachia-host interactions. However, parasite characteristics, such as the capacity to disturb host mitosis, and the ability to be horizontally transferred between hosts, also appear to play a role in this diversity. 相似文献
78.
Effect of anoxia and reoxygenation on antioxidant enzyme activities in immortalized brain endothelial cells 总被引:1,自引:0,他引:1
Olivier Rabin Michèle Piciotti Katy Drieu Jean-Marie Bourre Françoise Roux 《In vitro cellular & developmental biology. Animal》1996,32(4):221-224
Summary The effects of anoxia and reoxygenation on major antioxidant enzyme activities were investigatedin vitro in immortalized rat brain endothelial cells (RBE4 cells). A sublethal anoxic period of 12 h was assessed for RBE4 cells using the neutral red uptake test. Anoxia markedly influenced the specific activity of catalase and superoxide dismutase,
with no major effect on glutathione peroxidase or glutathione reductase. After 24 h postanoxia, the superoxide dismutase activity
modulated by the presence or absence of oxygen returned to control value.
Damage and recovery of RBE4 immortalized rat brain endothelial cells in culture after exposure to free radicals and other oxygen-derived species provides
a usefulin vitro model to study anoxia-reoxygenation trauma at the cellular level. 相似文献
79.
Summary In the laboratory, the two species of copepodsLepeophtheirus thompsoni andLepeophtheirus europaensis, ectoparasites of flatfishes, can meet and mate on at least one host species. In the wild however, these two species are found isolated on their sympatric hosts. Habitat selection theoretically represents a powerful enough mechanism to explain the maintenance of genetic heterogeneity in the wide sense. In this paper, the host colonization process is studied for both parasite species. It is shown that each parasite can develop and reach adult age on each host species. However,L. thompsoni is highly selective; it almost totally refuses to colonize hosts other than its natural one.Lepeophtheirus europaensis, on the contrary, readily infests turbot and brill in single-host experiments, but strongly prefers the brill when it has a choice. It appears that these two genetic entities are sympatrically maintained due to strong habitat selection. Such a pattern could theoretically only occur in a soft-selection context (density dependence). This point is discussed with respect to the different patterns in host use found in the geographical distribution of these parasites. 相似文献
80.
Marc Pauly Isabelle Kayser Martine Schmitz Fernand Ries François Hentges Mario Dicato 《Journal of molecular evolution》1995,41(6):974-978
The mdr1 gene, first member of the human multidrug-resistance gene family, is a major gene involved in cellular resistance to several drugs used in anticancer chemotherapy. Its product, the drug-excreting P-glycoprotein, shows a bipartite structure formed by two similar adjacent halves. According to one hypothesis, the fusion of two related ancestral genes during evolution could have resulted in this structure. The DNA sequence analysis of the introns located in the region connecting the two halves of the human mdr1 gene revealed a highly conserved poly(CA) · poly (TG) sequence in intron 15 and repeated sequences of the Alu family in introns 14 and 17. These repeated sequences most likely represent molecular fossils of ancient DNA elements which were involved in such a recombination event.
Correspondence to: M. Pauly 相似文献