全文获取类型
收费全文 | 18025篇 |
免费 | 1708篇 |
国内免费 | 3312篇 |
出版年
2024年 | 64篇 |
2023年 | 308篇 |
2022年 | 703篇 |
2021年 | 1105篇 |
2020年 | 908篇 |
2019年 | 1002篇 |
2018年 | 858篇 |
2017年 | 655篇 |
2016年 | 899篇 |
2015年 | 1353篇 |
2014年 | 1545篇 |
2013年 | 1607篇 |
2012年 | 1981篇 |
2011年 | 1742篇 |
2010年 | 1115篇 |
2009年 | 1083篇 |
2008年 | 1121篇 |
2007年 | 906篇 |
2006年 | 806篇 |
2005年 | 656篇 |
2004年 | 527篇 |
2003年 | 465篇 |
2002年 | 356篇 |
2001年 | 251篇 |
2000年 | 199篇 |
1999年 | 196篇 |
1998年 | 111篇 |
1997年 | 85篇 |
1996年 | 83篇 |
1995年 | 70篇 |
1994年 | 45篇 |
1993年 | 30篇 |
1992年 | 36篇 |
1991年 | 37篇 |
1990年 | 22篇 |
1989年 | 21篇 |
1988年 | 11篇 |
1987年 | 17篇 |
1986年 | 9篇 |
1985年 | 11篇 |
1984年 | 8篇 |
1983年 | 10篇 |
1982年 | 10篇 |
1981年 | 2篇 |
1964年 | 2篇 |
1959年 | 1篇 |
1957年 | 1篇 |
1956年 | 1篇 |
1953年 | 1篇 |
1950年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 296 毫秒
991.
A previously developed biosensor for fast estimation of short-term biochemical oxygen demand (BODst) was used for off-line monitoring of intermediate products from the initial step of an anaerobic process in laboratory scale. Good agreement was generally achieved between the results from the biosensor method and the conventional 5-day test except for samples with high content of organic polymers. During the period of agreement between the measurement principles, good correlation was achieved between the biogas production rate and the organic loading rate. The results from this study demonstrate that BODst can be a successful monitoring parameter to achieve a better process control. 相似文献
992.
When gratings moving in different directions are presented separately to the two eyes, we typically perceive periods of the combination of motion in the two eyes as well as periods of one or the other monocular motions. To investigate whether such interocular motion combination is determined by the intersection-of-constraints (IOC) or vector average mechanism, we recorded both optokinetic nystagmus eye movements (OKN) and perception during dichoptic presentation of moving gratings and random-dot patterns with various differences of interocular motion direction. For moving gratings, OKN alternately tracks not only the direction of the two monocular motions but also the direction of their combined motion. The OKN in the combined motion direction is highly correlated with the perceived direction of combined motion; its velocity complies with the IOC rule rather than the vector average of the dichoptic motion stimuli. For moving random-dot patterns, both OKN and perceived motion alternate only between the directions of the two monocular motions. These results suggest that interocular motion combination in dichoptic gratings is determined by the IOC and depends on their form. 相似文献
993.
Efficient inference of haplotypes from genotypes on a pedigree 总被引:1,自引:0,他引:1
We study haplotype reconstruction under the Mendelian law of inheritance and the minimum recombination principle on pedigree data. We prove that the problem of finding a minimum-recombinant haplotype configuration (MRHC) is in general NP-hard. This is the first complexity result concerning the problem to our knowledge. An iterative algorithm based on blocks of consecutive resolved marker loci (called block-extension) is proposed. It is very efficient and can be used for large pedigrees with a large number of markers, especially for those data sets requiring few recombinants (or recombination events). A polynomial-time exact algorithm for haplotype reconstruction without recombinants is also presented. This algorithm first identifies all the necessary constraints based on the Mendelian law and the zero recombinant assumption, and represents them using a system of linear equations over the cyclic group Z2. By using a simple method based on Gaussian elimination, we could obtain all possible feasible haplotype configurations. A C++ implementation of the block-extension algorithm, called PedPhase, has been tested on both simulated data and real data. The results show that the program performs very well on both types of data and will be useful for large scale haplotype inference projects. 相似文献
994.
Impaired insulin secretion and glucose tolerance in beta cell-selective Ca(v)1.2 Ca2+ channel null mice 下载免费PDF全文
Schulla V Renström E Feil R Feil S Franklin I Gjinovci A Jing XJ Laux D Lundquist I Magnuson MA Obermüller S Olofsson CS Salehi A Wendt A Klugbauer N Wollheim CB Rorsman P Hofmann F 《The EMBO journal》2003,22(15):3844-3854
Insulin is secreted from pancreatic beta cells in response to an elevation of cytoplasmic Ca(2+) resulting from enhanced Ca(2+) influx through voltage-gated Ca(2+) channels. Mouse beta cells express several types of Ca(2+) channel (L-, R- and possibly P/Q-type). beta cell-selective ablation of the gene encoding the L-type Ca(2+) channel subtype Ca(v)1.2 (betaCa(v)1.2(-/-) mouse) decreased the whole-cell Ca(2+) current by only approximately 45%, but almost abolished first-phase insulin secretion and resulted in systemic glucose intolerance. These effects did not correlate with any major effects on intracellular Ca(2+) handling and glucose-induced electrical activity. However, high-resolution capacitance measurements of exocytosis in single beta cells revealed that the loss of first-phase insulin secretion in the betaCa(v)1.2(-/-) mouse was associated with the disappearance of a rapid component of exocytosis reflecting fusion of secretory granules physically attached to the Ca(v)1.2 channel. Thus, the conduit of Ca(2+) entry determines the ability of the cation to elicit secretion. 相似文献
995.
996.
Gu JJ Tolin AK Jain J Huang H Santiago L Mitchell BS 《Molecular and cellular biology》2003,23(18):6702-6712
Inosine 5'-monophosphate dehydrogenase (IMPDH) is the critical, rate-limiting enzyme in the de novo biosynthesis pathway for guanine nucleotides. Two separate isoenzymes, designated IMPDH types I and II, contribute to IMPDH activity. An additional pathway salvages guanine through the activity of hypoxanthine-guanine phosphoribosyltransferase (HPRT) to supply the cell with guanine nucleotides. In order to better understand the relative contributions of IMPDH types I and II and HPRT to normal biological function, a mouse deficient in IMPDH type I was generated by standard gene-targeting techniques and bred to mice deficient in HPRT or heterozygous for IMPDH type II. T-cell activation in response to anti-CD3 plus anti-CD28 antibodies was significantly impaired in both single- and double-knockout mice, whereas a more general inhibition of proliferation in response to other T- and B-cell mitogens was observed only in mice deficient in both enzymes. In addition, IMPDH type I(-/-) HPRT(-/0) splenocytes showed reduced interleukin-4 production and impaired cytolytic activity after antibody activation, indicating an important role for guanine salvage in supplementing the de novo synthesis of guanine nucleotides. We conclude that both IMPDH and HPRT activities contribute to normal T-lymphocyte activation and function. 相似文献
997.
Defective gene expression,S phase progression,and maturation during hematopoiesis in E2F1/E2F2 mutant mice 总被引:6,自引:0,他引:6 下载免费PDF全文
E2F plays critical roles in cell cycle progression by regulating the expression of genes involved in nucleotide synthesis, DNA replication, and cell cycle control. We show that the combined loss of E2F1 and E2F2 in mice leads to profound cell-autonomous defects in the hematopoietic development of multiple cell lineages. E2F2 mutant mice show erythroid maturation defects that are comparable with those observed in patients with megaloblastic anemia. Importantly, hematopoietic defects observed in E2F1/E2F2 double-knockout (DKO) mice appear to result from impeded S phase progression in hematopoietic progenitor cells. During DKO B-cell maturation, differentiation beyond the large pre-BII-cell stage is defective, presumably due to failed cell cycle exit, and the cells undergo apoptosis. However, apoptosis appears to be the consequence of failed maturation, not the cause. Despite the accumulation of hematopoietic progenitor cells in S phase, the combined loss of E2F1 and E2F2 results in significantly decreased expression and activities of several E2F target genes including cyclin A2. Our results indicate specific roles for E2F1 and E2F2 in the induction of E2F target genes, which contribute to efficient expansion and maturation of hematopoietic progenitor cells. Thus, E2F1 and E2F2 play essential and redundant roles in the proper coordination of cell cycle progression with differentiation which is necessary for efficient hematopoiesis. 相似文献
998.
Involvement of the ubiquitin-proteasome system in the early stages of wallerian degeneration 总被引:15,自引:0,他引:15
Local axon degeneration is a common pathological feature of many neurodegenerative diseases and peripheral neuropathies. While it is believed to operate with an apoptosis-independent molecular program, the underlying molecular mechanisms are largely unknown. In this study, we used the degeneration of transected axons, termed "Wallerian degeneration," as a model to examine the possible involvement of the ubiquitin proteasome system (UPS). Inhibiting UPS activity by both pharmacological and genetic means profoundly delays axon degeneration both in vitro and in vivo. In addition, we found that the fragmentation of microtubules is the earliest detectable change in axons undergoing Wallerian degeneration, which among other degenerative events, can be delayed by proteasome inhibitors. Interestingly, similar to transected axons, degeneration of axons from nerve growth factor (NGF)-deprived sympathetic neurons could also be suppressed by proteasome inhibitors. Our findings suggest a possibility that inhibiting UPS activity may serve to retard axon degeneration in pathological conditions. 相似文献
999.
Xu Y Circolo A Jing H Wang Y Narayana SV Volanakis JE 《The Journal of biological chemistry》2000,275(1):378-385
Factor B is a serine protease, which despite its trypsin-like specificity has Asn instead of the typical Asp at the bottom of the S(1) pocket (position 189, chymotrypsinogen numbering). Asp residues are present at positions 187 and 226 and either one could conceivably provide the negative charge for binding the P(1)-Arg of the substrate. Determination of the crystal structure of the factor B serine protease domain has revealed that the side chain of Asp(226) is within the S(1) pocket, whereas Asp(187) is located outside the pocket. To investigate the possible role of these atypical structural features in substrate binding and catalysis, we constructed a panel of mutants of these residues. Replacement of Asp(187) caused moderate (50-60%) decrease in hemolytic activity, compared with wild type factor B, whereas replacement of Asn(189) resulted in more profound reductions (71-95%). Substitutions at these two positions did not significantly affect assembly of the alternative pathway C3 convertase. In contrast, elimination of the negative charge from Asp(226) completely abrogated hemolytic activity and also affected formation of the C3 convertase. Kinetic analyses of the hydrolysis of a P(1)-Arg containing thioester by selected mutants confirmed that residue Asp(226) is a primary structural determinant for P(1)-Arg binding and catalysis. 相似文献
1000.
The influence of aerated hydration seed treatment on seed longevity as assessed by the viability equations 总被引:2,自引:0,他引:2
Powell AA Yule LJ Jing HC Groot SP Bino RJ Pritchard HW 《Journal of experimental botany》2000,51(353):2031-2043
Aerated hydration (AH) treatments of cauliflower seeds for 12 h (12AH) and 28 h (28AH) at 20 degrees C resulted in improved or reduced storage potential of low or high vigour seeds, respectively. Seeds were stored at their initial seed moisture content (mean 5.5% mc) or at 12% mc at 10 degrees C for 12 months and at 20 degrees C for 4 months. The improved longevity of low vigour seeds was associated with increased K(i) (initial seed viability) and a reduced rate of deterioration (1/sigma) whereas the K(i) of high vigour seeds fell after 28AH and the rate of deterioration increased such that the time to lose one probit of viability decreased from 28.7 to 5.3 months at 10 degrees C and from 10.4 to 1.2 months at 20 degrees C. The improved K(i) of low vigour seeds could be explained by the reduction in the extent of deterioration after AH, as indicated by the increase in germination after cotrolled deterioration (CD), and the possible activation of metabolic repair during treatment. In contrast the reduced germination after CD of AH-treated high vigour seeds was indicative of deterioration as a result of treatment. Both high and low vigour seeds contained constitutive levels of ss-tubulin which increased during AH treatment, the increase being greater in high vigour seeds. High vigour seeds also showed an increase in the proportion of nuclear DNA present as 4C DNA, from 3% (untreated seeds) to 26% (28AH), indicative of germination advancement from the G(1) to G(2) phase of the cell cycle during treatment. This higher proportion of 4C DNA is correlated with the increased sensitivity of seeds to drying and/or storage after AH, leading to their reduced K(i) and storage potential. In contrast, there was little change in %4C in low vigour seeds. Priming in polyethylene glycol (PEG, -1.0 MPa) for 5 d or 13 d also improved the longevity of low vigour seeds stored at their initial and 12% mc at 10 degrees C for 8 months, as reflected in their laboratory and CD germination. In this case, however, the improved longevity of the low vigour seeds following 13 d priming was associated with an increase in 4C DNA from 4% (dry control) to 56% after treatment. The germination of both untreated and primed high vigour seeds remained high throughout the storage period. Increases in the rate of germination (decreased mean germination time) observed after all AH and PEG treatments were not consistently associated with an increase in the proportion of nuclei containing 4C DNA. 相似文献