全文获取类型
收费全文 | 2164篇 |
免费 | 348篇 |
国内免费 | 2篇 |
专业分类
2514篇 |
出版年
2021年 | 30篇 |
2016年 | 27篇 |
2015年 | 58篇 |
2014年 | 63篇 |
2013年 | 70篇 |
2012年 | 79篇 |
2011年 | 93篇 |
2010年 | 69篇 |
2009年 | 52篇 |
2008年 | 80篇 |
2007年 | 94篇 |
2006年 | 79篇 |
2005年 | 45篇 |
2004年 | 65篇 |
2003年 | 74篇 |
2002年 | 49篇 |
2001年 | 67篇 |
2000年 | 67篇 |
1999年 | 62篇 |
1998年 | 26篇 |
1997年 | 25篇 |
1996年 | 31篇 |
1995年 | 25篇 |
1993年 | 25篇 |
1992年 | 47篇 |
1991年 | 32篇 |
1990年 | 45篇 |
1989年 | 39篇 |
1988年 | 35篇 |
1987年 | 39篇 |
1986年 | 58篇 |
1985年 | 57篇 |
1984年 | 45篇 |
1983年 | 33篇 |
1982年 | 35篇 |
1981年 | 30篇 |
1980年 | 19篇 |
1979年 | 51篇 |
1978年 | 48篇 |
1977年 | 38篇 |
1976年 | 25篇 |
1975年 | 25篇 |
1974年 | 41篇 |
1973年 | 32篇 |
1972年 | 29篇 |
1971年 | 33篇 |
1970年 | 19篇 |
1969年 | 28篇 |
1968年 | 18篇 |
1967年 | 22篇 |
排序方式: 共有2514条查询结果,搜索用时 15 毫秒
11.
12.
Synthesis and processing of alpha-galactosidase A in human fibroblasts. Evidence for different mutations in Fabry disease 总被引:6,自引:0,他引:6
P Lemansky D F Bishop R J Desnick A Hasilik K von Figura 《The Journal of biological chemistry》1987,262(5):2062-2065
The synthesis and processing of the human lysosomal enzyme alpha-galactosidase A was examined in normal and Fabry fibroblasts. In normal cells, alpha-galactosidase A was synthesized as an Mr = 50,500 precursor, which contained phosphate groups in oligosaccharide chains cleavable by endoglucosaminidase H. The precursor was processed via ill-defined intermediates to a mature Mr 46,000 form. Processing was complete within 3-7 days after synthesis. In the presence of NH4Cl and in I-cell fibroblasts, the majority of newly synthesized alpha-galactosidase A was secreted as an Mr = 52,000 form. For comparison, the processing and stability of alpha-galactosidase A were examined in fibroblasts from five unrelated patients with Fabry disease, which is caused by deficient alpha-galactosidase A activity. In one cell line, synthesis of immunologically cross-reacting polypeptides was not detectable. In another, the synthesis, processing, and stability of alpha-galactosidase A was indistinguishable from that in normal fibroblasts. In a third Fabry cell line, the mutation retarded the maturation of alpha-galactosidase A. Finally, in two cell lines, alpha-galactosidase A polypeptides were synthesized that were rapidly degraded following delivery to lysosomes. These results clearly indicate that Fabry disease comprises a heterogeneous group of mutations affecting synthesis, processing, and stability of alpha-galactosidase A. 相似文献
13.
Body masses of 3,739 birds representing immature and adult males and females of 15 species of passeriforms (both uninfected and infected with Haemoproteus spp. and Leucocytozoon spp.) were compared. There was some interaction among year, month and area of capture for several host species, but there was no discernible effect of either parasite genus on body mass. There were no effects due to high intensity parasitemia for eight host species examined. Either parasitism does not cause loss of body mass, or the techniques used were too insensitive to separate effects of parasitism from other natural causes. 相似文献
14.
C Fittschen R T Parmley S P Bishop J C Williams 《The American journal of anatomy》1988,181(2):195-202
During neutrophil granule genesis, the formation of primary granules is generally thought to be limited to the promyelocyte stage; whereas synthesis of secondary granules is thought to occur only at the myelocyte stage. This hypothesis was tested morphometrically in feline neutrophils that are known to contain both granule types. Marrow specimens obtained from six cats were stained with peroxidase for identification of neutrophil primary granules and counterstained with periodic acid-thiocarbohydrazide-silver proteinate (PA-TCH-SP) for identification of secondary granules. By regression analysis using arithmetic models, numbers of cytoplasmic granules in 311 cells were correlated with the degree of nuclear chromatin condensation, which was shown to be an adequate parameter for cell maturation. Promyelocytes and myelocytes had similar mean numbers of peroxidase-positive granules per unit area. A significant increase (p less than or equal to 0.0001) in the numbers of peroxidase-positive granules was noted between the metamyelocyte and the mature neutrophil stage, despite the lack of peroxidase activity in endoplasmic reticulum and Golgi lamellae. By contrast, a significant increase of peroxidase-negative granules between the metamyelocyte and the mature neutrophil stage was not clearly established with these methods. The increase in peroxidase-positive granules may indicate continued production of peroxidase-containing granules and/or redistribution of peroxidase among lysosomal organelles in late feline neutrophils. 相似文献
15.
Trinitrophenyladenosine monophosphate (TNP-AMP) binding to the phosphorylated Ca2+-ATPase of sarcoplasmic reticulum results in manyfold higher fluorescence intensity and longer lifetimes of the nucleotide analogue, as compared to TNP-AMP binding to the nonphosphorylated enzyme. This is observed when the phosphoenzyme intermediate is formed either from ATP or from inorganic phosphate (Pi). An important question is whether the TNP-AMP fluorescence properties can also reflect the kinetically defined interconversions of different phosphoenzyme species during catalysis. We have approached this question by manipulating the phosphorylation conditions in a manner which is known to result in accumulation of different species of the phosphoenzyme, i.e., by variations in pH, substrates, and K+ and Ca2+ concentrations. Decreasing pH or increasing [K+] caused large decreases in fluorescence intensity at a given concentration of TNP-AMP under conditions of phosphorylation with either ATP or Pi. In contrast, low to high intravesicular Ca2+ concentrations had no effect on fluorescence during steady-state turnover. TNP-AMP titrations of the phosphorylated enzyme stabilized in different states revealed that H+ and K+ caused a shift in TNP-AMP binding affinity to the site responsible for high fluorescence enhancement, while maintaining approximately the same maximal fluorescence yield at saturation. The fluorescence lifetimes of TNP-AMP bound to phosphoenzyme did not change with variations in pH, [K+], and substrates. We conclude that the environment of that part of the TNP-AMP binding site which binds the trinitrophenyl moiety undergoes a change upon enzyme phosphorylation resulting in enhanced fluorescence yield; this change is invariant between different phosphoenzyme species.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
16.
Tn5-induced mutants of Azotobacter vinelandii affected in nitrogen fixation under Mo-deficient and Mo-sufficient conditions 总被引:14,自引:8,他引:6 下载免费PDF全文
Mutants of Azotobacter vinelandii affected in N2 fixation in the presence of 1 microM Na2MoO4 (conventional system), 50 nM V2O5, or under Mo deficiency (alternative system) have been isolated after Tn5 mutagenesis with the suicide plasmid pSUP1011. These mutants can be grouped into at least four broad phenotypic classes. Mutants in the first class are Nif- under Mo sufficiency but Nif+ under Mo deficiency or in the presence of V2O5. A nifk mutant and a mutant apparently affected in regulation of the conventional system belong to this class. Mutants in the second class are Nif- under all conditions. An FeMo-cofactor-negative mutant (NifB-) belongs to this class, implying an involvement of nifB in both the conventional and the alternative N2 fixation systems. The third mutant class consists of mutants incapable of N2-dependent growth under Mo deficiency. Most of the mutants in this class are also affected in N2 fixation in the presence of 1 microM Na2MoO4, with acetylene reduction rates ranging from 28 to 51% of the rates of the wild type. Strains constructed by genetic transfer of the Kanr marker of mutants from this class into nifHDK or nifK deletion mutants showed N2-dependent growth only in the presence of V2O5, suggesting that growth in the presence of V2O5 and growth under Mo deficiency are independent phenomena. The only mutant in the fourth class shows wild-type nitrogenase activity under Mo sufficiency, but only 10% of the acetylene reduction activity of the wild type in the presence of 50 nM V2O5. The acetylene reduction rates of whole cells of this mutant are identical in Mo-deficient medium and in medium containing V2O5. The conventional nitrogenase subunits are expressed in this mutant even under Mo deficiency or in the presence of V2O5; however, the NH4+- and Mo-repressible proteins normally seen under these conditions could not be detected on two-dimensional gels. The Tn5 insertion carried by this mutant makes N2 fixation dependent solely on the conventional system and consequently abolishes the vanadium effect. 相似文献
17.
Quantitative measurement of sn-1,2-diacylglycerols present in platelets, hepatocytes, and ras- and sis-transformed normal rat kidney cells 总被引:82,自引:0,他引:82
J Preiss C R Loomis W R Bishop R Stein J E Niedel R M Bell 《The Journal of biological chemistry》1986,261(19):8597-8600
A simple enzymatic method for the quantitation of the mass of sn-1,2-diacylglycerol (DAG) present in crude lipid extracts was developed to assess the function of DAGs as intracellular "second messengers" of extracellular agents and of oncogene products. The assay employed Escherichia coli DAG kinase which constituted approximately 15% of the membrane protein of a plasmid-bearing strain and defined mixed micellar conditions to solubilize the DAG present and allow its quantitative conversion to [32P]phosphatidic acid. The assay was proportional with the amount of DAG added over the range of 25 pmol to 25 nmol. The rapid rise of DAG in platelets stimulated with thrombin (210% over basal) and in hepatocytes stimulated with vasopressin (230% over basal) was quantitated and the values agreed with previous measurements. The amounts of DAG in normal rat kidney (NRK) cells grown at 34 and 38 degrees C, respectively, were 0.47 and 0.61 nmol/100 nmol of phospholipid. In K-ras-transformed NRK cells grown at 34 or 38 degrees C, DAG levels were elevated 168 or 138%, respectively. When a temperature-sensitive K-ras NRK cell line was investigated, the amount of DAG present was elevated at the permissive but not at the restrictive temperature. These data are consistent with the K-ras protein functioning in transmembrane signalling by activating phospholipase C. Protein kinase C (Ca2+/phospholipid-dependent enzyme) activation by DAG may play an important role in cellular transformation. 相似文献
18.
Arterial and cardiopulmonary reflexes in the regulation of the neurohumoral drive to the circulation 总被引:2,自引:0,他引:2
The integrative reflex control of the neurohumoral drive to the circulation by unmyelinated vagal afferents and arterial baroreceptor afferents is often complex and depends on a number of factors. These include 1) the initial condition or the existing inhibitory influence exerted by one receptor station, 2) alteration in gain or central response of one reflex as a result of afferent information from the other system, and 3) altered receptor sensitivity as a result of reflex changes in sympathetic outflow. With respect to the cardiopulmonary and arterial baroreflex control of renin release, the accompanying reflex hemodynamic changes may influence the magnitude of the renin response. Finally, recent data suggest that reflex increases in vasopressin by either reflex system may result in an inhibitory influence on sympathetic outflow. Thus, in this latter case, a central interaction results between two reflex responses. 相似文献
19.
A semi-natural Drosophila melanogaster population was twice forced through a genetic bottleneck and allowed to recover naturally. In one case additional variation was introduced to the recovering population. The percentage of lethal chromosomes, the level of allelism between these lethals, and the effective population size calculated from the allelism of these lethals all rose sharply in the few generations following each bottleneck, though this was not the case in the very first generation. Thereafter this rise decelerated rapidly and never returned to pre-bottleneck levels. Additional introduced variation had little effect. The reasons for and implications of this pattern have been considered. 相似文献
20.
Assembly of the endoplasmic reticulum phospholipid bilayer: the phosphatidylcholine transporter 总被引:12,自引:0,他引:12
Phospholipids are synthesized and concomitantly inserted on the cytoplasmic surface of the endoplasmic reticulum. Assembly of the phospholipid bilayer requires translocation to the lumenal monolayer. The hypothesis that rat liver microsomes contain a protein transporter, or "flippase," for phosphatidylcholine was tested by measuring the transport of sn-1,2,-dibutyroylphosphatidylcholine (diC4PC). This homolog retains the polar head group, the portion of the phospholipid unable to undergo spontaneous transmembrane movement in vesicles, and its water solubility permits application of standard transport methods. DiC4PC entered the lumenal compartment of microsomal vesicles. Transport was saturable and was dependent on time, amount of microsomes, and an intact permeability barrier. DiC4PC transport was inhibited by structural analogs (but not by sn-2,3-diC4PC) and by treatment of microsomes with proteases, N-ethylmaleimide, and trinitrobenzenesulfonic acid. These data suggest that the transmicrosomal movement of diC4PC is protein mediated. DiC4PC was not transported across PC vesicles or red cell membranes, where PC translocation is slow. 相似文献