全文获取类型
收费全文 | 2890篇 |
免费 | 218篇 |
国内免费 | 9篇 |
专业分类
3117篇 |
出版年
2022年 | 18篇 |
2021年 | 57篇 |
2020年 | 30篇 |
2019年 | 36篇 |
2018年 | 54篇 |
2017年 | 36篇 |
2016年 | 68篇 |
2015年 | 94篇 |
2014年 | 124篇 |
2013年 | 178篇 |
2012年 | 215篇 |
2011年 | 204篇 |
2010年 | 131篇 |
2009年 | 114篇 |
2008年 | 145篇 |
2007年 | 140篇 |
2006年 | 125篇 |
2005年 | 111篇 |
2004年 | 126篇 |
2003年 | 129篇 |
2002年 | 99篇 |
2001年 | 37篇 |
2000年 | 38篇 |
1999年 | 40篇 |
1998年 | 35篇 |
1997年 | 33篇 |
1996年 | 26篇 |
1995年 | 27篇 |
1994年 | 26篇 |
1993年 | 33篇 |
1992年 | 42篇 |
1991年 | 16篇 |
1990年 | 17篇 |
1989年 | 23篇 |
1988年 | 14篇 |
1987年 | 25篇 |
1986年 | 15篇 |
1985年 | 19篇 |
1983年 | 17篇 |
1982年 | 17篇 |
1981年 | 12篇 |
1980年 | 15篇 |
1979年 | 13篇 |
1978年 | 13篇 |
1977年 | 15篇 |
1976年 | 14篇 |
1975年 | 12篇 |
1973年 | 14篇 |
1972年 | 15篇 |
1970年 | 21篇 |
排序方式: 共有3117条查询结果,搜索用时 0 毫秒
41.
Tuo Li Annika J. E. Borg Leo Krammer Rolf Breinbauer Bernd Nidetzky 《Biotechnology and bioengineering》2023,120(6):1506-1520
Polyphenolic aglycones featuring two sugars individually attached via C-glycosidic linkage (di-C-glycosides) represent a rare class of plant natural products with unique physicochemical properties and biological activities. Natural scarcity of such di-C-glycosides limits their use-inspired exploration as pharmaceutical ingredients. Here, we show a biocatalytic process technology for reaction-intensified production of the di-C-β-glucosides of two representative phenol substrates, phloretin (a natural flavonoid) and phenyl-trihydroxyacetophenone (a phenolic synthon for synthesis), from sucrose. The synthesis proceeds via an iterative two-fold C-glycosylation of the respective aglycone, supplied as inclusion complex with 2-hydroxypropyl β-cyclodextrin for enhanced water solubility of up to 50 mmol/L, catalyzed by a kumquat di-C-glycosyltransferase (di-CGT), and it uses UDP-Glc provided in situ from sucrose by a soybean sucrose synthase, with catalytic amounts (≤3 mol%) of UDP added. Time course analysis reveals the second C-glycosylation as rate-limiting (0.4–0.5 mmol/L/min) for the di-C-glucoside production. With internal supply from sucrose keeping the UDP-Glc at a constant steady-state concentration (≥50% of the UDP added) during the reaction, the di-C-glycosylation is driven to completion (≥95% yield). Contrary to the mono-C-glucoside intermediate which is stable, the di-C-glucoside requires the addition of reducing agent (10 mmol/L 2-mercaptoethanol) to prevent its decomposition during the synthesis. Both di-C-glucosides are isolated from the reaction mixtures in excellent purity (≥95%), and their expected structures are confirmed by NMR. Collectively, this study demonstrates efficient glycosyltransferase cascade reaction for flexible use in natural product di-C-β-glucoside synthesis from expedient substrates. 相似文献
42.
Patrick Diep Heping Leo Shen Julian A. Wiesner Nadia Mykytczuk Vladimiros Papangelakis Alexander F. Yakunin Radhakrishnan Mahadevan 《Engineering in Life Science》2023,23(7):2200133
Mine wastewater often contains dissolved metals at concentrations too low to be economically extracted by existing technologies, yet too high for environmental discharge. The most common treatment is chemical precipitation of the dissolved metals using limestone and subsequent disposal of the sludge in tailing impoundments. While it is a cost-effective solution to meet regulatory standards, it represents a lost opportunity. In this study, we engineered Escherichia coli to overexpress its native NikABCDE transporter and a heterologous metallothionein to capture nickel at concentrations in local effluent streams. We found the engineered strain had a 7-fold improvement in the bioaccumulation performance for nickel compared to controls, but also observed a drastic decrease in cell viability due to metabolic burden or inducer (IPTG) toxicity. Growth kinetic analysis revealed the IPTG concentrations used based on past studies lead to growth inhibition, thus delineating future avenues for optimization of the engineered strain and its growth conditions to perform in more complex environments. 相似文献
43.
Vaccinium section Cyanococcus comprises diploid, tetraploid, and hexaploid species (x = 12) all of which are highly self-sterile. In order to assess the distribution of genetic variation within and among the diploids, population genetic analyses of allozyme data were conducted on three species: V. elliottii, V. myrtilloides, and V. tenellum. Populations were located throughout the range of these taxa in eastern North America. Data were collected at 20 loci, 12 of which are mendelian based on formal genetic analyses. Consistent with expectations for out-crossing taxa, these species exhibited high levels of variation within populations. Eighteen loci were polymorphic with the number and frequency of alleles varying among taxa. Mean values for the number of alleles per polymorphic locus, proportion of polymorphic loci, and expected heterozygosity were 2.8, 48.2, and 0.148, respectively. High infraspecific genetic identities exceeding 0.9 indicated that these taxa are homogeneous. All populations were in Hardy-Weinberg equilibrium with slight heterozygote excess observed in V. myrtilloides and V. tenellum. Although total genetic diversity was lower than that observed for other predominantly out-crossing species, it was apportioned similarly. The majority could be attributed to differences among individuals within populations. Conspecific populations were relatively undifferentiated with genetic differentiation similar to other self-incompatible species. 相似文献
44.
M Valente P de Martino Rosaroll C De Santo S Di Meo T De Leo 《Archives internationales de physiologie et de biochimie》1989,97(6):427-430
Confirming the literature data the authors describe that the heart rate is smaller in the newborn rats than in adult ones and increases until the adult values during the first two weeks of life. On the other hand, the blood thyroid hormone exhibits the same pattern, showing an early postnatal increment. As, according the Adolph's data (1967), the heart rate enhancement is not due to the catecholamines, the authors suppose that such enhancement might conceivably depend on thyroid hormone increment. 相似文献
45.
Karri Silventoinen Sampo Sammalisto Markus Perola Dorret I Boomsma Belinda K Cornes Chayna Davis Leo Dunkel Marlies De Lange Jennifer R Harris Jacob V B Hjelmborg Michelle Luciano Nicholas G Martin Jakob Mortensen Lorenza Nisticò Nancy L Pedersen Axel Skytthe Tim D Spector Maria Antonietta Stazi Gonneke Willemsen Jaakko Kaprio 《Twin research》2003,6(5):399-408
A major component of variation in body height is due to genetic differences, but environmental factors have a substantial contributory effect. In this study we aimed to analyse whether the genetic architecture of body height varies between affluent western societies. We analysed twin data from eight countries comprising 30,111 complete twin pairs by using the univariate genetic model of the Mx statistical package. Body height and zygosity were self-reported in seven populations and measured directly in one population. We found that there was substantial variation in mean body height between countries; body height was least in Italy (177 cm in men and 163 cm in women) and greatest in the Netherlands (184 cm and 171 cm, respectively). In men there was no corresponding variation in heritability of body height, heritability estimates ranging from 0.87 to 0.93 in populations under an additive genes/unique environment (AE) model. Among women the heritability estimates were generally lower than among men with greater variation between countries, ranging from 0.68 to 0.84 when an additive genes/shared environment/unique environment (ACE) model was used. In four populations where an AE model fit equally well or better, heritability ranged from 0.89 to 0.93. This difference between the sexes was mainly due to the effect of the shared environmental component of variance, which appears to be more important among women than among men in our study populations. Our results indicate that, in general, there are only minor differences in the genetic architecture of height between affluent Caucasian populations, especially among men. 相似文献
46.
Expression of insulin-like growth factor II (IGF-II) and histological changes in the thymus and spleen of transgenic mice overexpressing IGF-II 总被引:2,自引:0,他引:2
Leo T. M. Van der Ven Paul J. M. Roholl Maria G. Reijnen-Gresnigt Ruud J. Bloemen Sylvia C. van Buul-Offers 《Histochemistry and cell biology》1997,107(3):193-203
Previously, transgenic mice were constructed overexpressing human insulin-like growth factor II (IGF-II) under control of
the H2kb promoter. The IGF-II transgene was highly expressed in thymus and spleen, and these organs showed an increase in weight. In
the current study we have analyzed the sites of IGF-II mRNA expression, the distribution of IGF-II, IGF-I, and both IGF receptors,
and histomorphometrical changes in thymus and spleen. With in situ mRNA hybridization, expression of the IGF-II transgene
is found with high intensity in the thymic medulla and in the white pulp/marginal zone of the spleen, whereas there were scattered
positive cells in the thymic cortex and in the splenic red pulp. Hybridization was restricted to non-lymphocytic cells. Immunohistochemistry
revealed intense IGF-II peptide staining with the same distribution as IGF-II mRNA. There was additional intense IGF-II staining
of all elements in the splenic red pulp (including trabeculae) and diffuse, low level staining in the thymic cortex. These
findings were not observed in control mice. In the thymic medulla, most IGF-II producing cells co-labelled with keratin, whereas
a minor population also stained for the monocyte/macrophage marker MOMA-2. In the spleen, co-labelling of IGF-II producing
cells was found with MOMA-1 (marginal zone), or with the dendritic cell marker NLDC-145 (red pulp). IGF-I and both IGF receptors
were found in these organs in nearly all cell types, with a similar pattern in transgenic mice and in control animals. Histomorphometric
analysis revealed a marked increase of thymus cortex size and an increased trabecular size in the spleen. This suggests that
IGF-II overproduction induces local effects (auto/paracrine) in the thymic cortex, but not in the thymic medulla. Trabecular
growth in the spleen most likely is a distant effect (paracrine or endocrine) of IGF-II overproduction.
Accepted: 5 September 1996 相似文献
47.
The unicellular green alga Chlamydomonas reinhardtii synthesizes glycerol as an osmoregulatory metabolite when exposed to high saline concentrations (200 mM NaCl). Response to osmotic stress can be used for biotechnological production of this compound. When synthesis of a substance is linked to photosynthetic capacity and consequently to effective light, the production on a large scale makes an efficient utilization of light necessary. In the present work a model for evaluation of effective light has been tested. 相似文献
48.
49.
Clinical phenotype of nephrogenic diabetes insipidus in females heterozygous for a vasopressin type 2 receptor mutation 总被引:2,自引:0,他引:2
Angenita F. van Lieburg Marian A. J. Verdijk Frans Schoute Marjolijn J. L. Ligtenberg Bernard A. van Oost Franz Waldhauser Maria Dobner Leo A. H. Monnens Nine V. A. M. Knoers 《Human genetics》1995,96(1):70-78
Nephrogenic diabetes insipidus (NDI) usually shows an X-linked recessive mode of inheritance caused by mutations in the vasopressin type 2 receptor gene (AVPR2). In the present study, three NDI families are described in which females show clinical features resembling the phenotype in males. Maximal urine osmolality in three female patients did not exceed 200 mosmol/kg and the absence of extra-renal responses to 1-desamino-8-d-arginine vasopressin was demonstrated in two of them. All affected females and two asymptomatic female family members were shown to be heterozygous for an AVPR2 mutation. Skewed X-inactivation is the most likely explanation for the clinical manifestation of NDI in female carriers of an AVPR2 mutation. It is concluded that, in female NDI patients, the possibility of heterozygosity for an AVPR2 gene mutation has to be considered in addition to homozygosity for mutations in the aquaporin 2 gene. 相似文献
50.
The phase behavior of isolated photoreceptor membrane lipids is further investigated by 31P-NMR, in view of earlier discrepant results [(1979) Biochim. Biophys. Acta 558, 330–337; (1982) FEBS Lett. 124, 93–99]. We present evidence that the discrepancy is due to bivalent cations. When resuspended in aqueous media at neutral pH in the absence of bivalent cations, the isolated photoreceptor membrane lipids largely adopt the bilayer configuration. However, upon addition of such cations (Ca2+ Mg2+) or when resuspended in their presence, the formation of other phases (hexagonal HII, lipidic particles) results. The rate of this transition depends on cation concentration and temperature. The transition is not easily reversed by addition of EDTA. Implications with regard to photoreceptor membrane structure and function need further study. 相似文献