全文获取类型
收费全文 | 3386篇 |
免费 | 216篇 |
专业分类
3602篇 |
出版年
2022年 | 16篇 |
2021年 | 32篇 |
2019年 | 28篇 |
2018年 | 37篇 |
2017年 | 35篇 |
2016年 | 76篇 |
2015年 | 92篇 |
2014年 | 130篇 |
2013年 | 132篇 |
2012年 | 221篇 |
2011年 | 246篇 |
2010年 | 185篇 |
2009年 | 140篇 |
2008年 | 185篇 |
2007年 | 187篇 |
2006年 | 166篇 |
2005年 | 171篇 |
2004年 | 150篇 |
2003年 | 174篇 |
2002年 | 157篇 |
2001年 | 38篇 |
2000年 | 27篇 |
1999年 | 55篇 |
1998年 | 58篇 |
1997年 | 45篇 |
1996年 | 57篇 |
1995年 | 40篇 |
1994年 | 43篇 |
1993年 | 31篇 |
1992年 | 52篇 |
1991年 | 30篇 |
1990年 | 42篇 |
1989年 | 28篇 |
1988年 | 20篇 |
1987年 | 16篇 |
1986年 | 14篇 |
1985年 | 18篇 |
1984年 | 27篇 |
1983年 | 23篇 |
1982年 | 30篇 |
1981年 | 32篇 |
1980年 | 21篇 |
1979年 | 34篇 |
1978年 | 19篇 |
1977年 | 19篇 |
1976年 | 18篇 |
1971年 | 15篇 |
1970年 | 16篇 |
1969年 | 13篇 |
1967年 | 14篇 |
排序方式: 共有3602条查询结果,搜索用时 0 毫秒
81.
Tsyganov VE Belimov AA Borisov AY Safronova VI Georgi M Dietz KJ Tikhonovich IA 《Annals of botany》2007,99(2):227-237
BACKGROUND AND AIMS: To date, there are no crop mutants described in the literature that display both Cd accumulation and tolerance. In the present study a unique pea (Pisum sativum) mutant SGECd(t) with increased Cd tolerance and accumulation was isolated and characterized. METHODS: Ethylmethane sulfonate mutagenesis of the pea line SGE was used to obtain the mutant. Screening for Cd-tolerant seedlings in the M2 generation was performed using hydroponics in the presence of 6 microm CdCl2. Hybridological analysis was used to identify the inheritance of the mutant phenotype. Several physiological and biochemical characteristics of SGECd(t) were studied in hydroponic experiments in the presence of 3 microm CdCl2, and elemental analysis was conducted. KEY RESULTS: The mutant SGECd(t) was characterized as having a monogenic inheritance and a recessive phenotype. It showed increased Cd concentrations in roots and shoots but no obvious morphological defects, demonstrating its capability to cope well with increased Cd levels in its tissues. The enhanced Cd accumulation in the mutant was accompanied by maintenance of homeostasis of shoot Ca, Mg, Zn and Mn contents, and root Ca and Mg contents. Through the application of La(+3) and the exclusion of Ca from the nutrient solution, maintenance of nutrient homeostasis in Cd-stressed SGECd(t) was shown to contribute to the increased Cd tolerance. Control plants of the mutant (i.e. no Cd treatment) had elevated concentrations of glutathione (GSH) in the roots. Through measurements of chitinase and guaiacol-dependent peroxidase activities, as well as proline and non-protein thiol (NPT) levels, it was shown that there were lower levels of Cd stress both in roots and shoots of SGECd(t). Accumulation of phytochelatins [(PCcalculated) = (NPT)-(GSH)] could be excluded as a cause of the increased Cd tolerance in the mutant. CONCLUSIONS: The SGECd(t) mutant represents a novel and unique model to study adaptation of plants to toxic heavy metal concentrations. 相似文献
82.
Implication of apoE isoforms in cholesterol metabolism by primary rat hippocampal neurons and astrocytes 总被引:3,自引:0,他引:3
Apolipoprotein E (apoE) has been genetically linked to late-onset Alzheimer's disease. From the three common alleles (epsilon2, epsilon3 and epsilon4), epsilon4 has been suggested to promote amyloid beta (Ass) plaque fibrillation, one hallmark of Alzheimer's disease. It has been demonstrated that altered lipid content of hippocampal plasma membrane coincides with the disease. In this study, we show for the first time that the apoE dependent cholesterol metabolism in hippocampal neurons is higher than that of hippocampal astrocytes. Further, apoE-bound cholesterol is highly incorporated in membranous compartments in hippocampal neurons, whereas hippocampal astrocytes show higher intracellular distribution. This is an effect that coincides with cell-type dependent difference of low density lipoprotein receptor (LDLR) family member expression. Hippocampal neurons express high levels of the LDLR related protein (LRP), whereas hippocampal astrocytes are highly positive for LDLR. We could also demonstrate an apoE isoform (apoE2, apoE3 and apoE4) dependent cholesterol uptake in both cells types. In hippocampal neurons, we could find a decreased apoE4-bound cholesterol uptake. In contrast, hippocampal astrocytes show decreased internalization of apoE2-bound cholesterol. In addition, lipidated apoE4 is little associated with neurites in hippocampal neurons in comparison to the other two isoforms. In contrary, hippocampal astrocytes show faint apoE2 immunocytostaining intensity. Data presented indicate that the role of apoE4 in cholesterol homeostasis and apolipoprotein cell association is more pronounced in hippocampal neurons, showing significant alterations compared to the other two isoforms, suggesting that hippocampal neurons are affected by apoE4 associated altered cholesterol metabolism compared to hippocampal astrocytes. 相似文献
83.
Manfred Braun Jong Min Kim Rolf D. Schmid 《Applied microbiology and biotechnology》1992,37(5):594-598
Summary The soil isolate Cellulomonas cellulans AM8 produces an extracellular l-amino acid oxidase (L-AAO) with broad substrate specificity. The strain produced up to 0.35 unit (U)/ml of the extracellular L-AAO in a simple medium containing glycerol and yeast extract. The enzyme was easily purified up to 30 U/mg protein using Phenyl-Sepharose fast flow. The purified enzyme migrated as single band on sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) with a molecular mass of 55 kDa. On native PAGE the molecular mass was approx. 300 000 kDa, which may be due to aggregation. With the exception of glycine, proline, and threonine, all the amino acids normally constituting proteins were oxidized. The V
max values from 0.7 to 35.2 U/mg for aspartic acid and lysine, respectively, and the K
m values from 0.007 to 7.1 mm for cysteine and valine, respectively, were obtained at 25° C and pH 7.0 in oxygen-saturated solutions. The L-AAO had a pH optimum of 6.5–7.5. It was stable for several months at — 30° C and for some days at 35° C. Ferricyanide served as an electron acceptor with a V
max of 50 U/mg and K
m for 0.3 mm with phenylalanine as the substrate.
Correspondence to: R. D. Schmid 相似文献
84.
Social parasites exploit the colony resources of social insects. Some of them exploit the host colony as a food resource or as a shelter whereas other species also exploit the brood care behavior of their social host. Some of these species have even lost the worker caste and rely completely on the host''s worker force to rear their offspring. To avoid host defenses and bypass their recognition code, these social parasites have developed several sophisticated chemical infiltration strategies. These infiltration strategies have been highly studied in several hymenopterans. Once a social parasite has successfully entered a host nest and integrated its social system, its emerging offspring still face the same challenge of avoiding host recognition. However, the strategy used by the offspring to survive within the host nest without being killed is still poorly documented. In cuckoo bumblebees, the parasite males completely lack the morphological and chemical adaptations to social parasitism that the females possess. Moreover, young parasite males exhibit an early production of species-specific cephalic secretions, used as sexual pheromones. Host workers might thus be able to recognize them. Here we used a bumblebee host-social parasite system to test the hypothesis that social parasite male offspring exhibit a chemical defense strategy to escape from host aggression during their intranidal life. Using behavioral assays, we showed that extracts from the heads of young cuckoo bumblebee males contain a repellent odor that prevents parasite males from being attacked by host workers. We also show that social parasitism reduces host worker aggressiveness and helps parasite offspring acceptance. 相似文献
85.
Collagen and mature elastic fibre organisation as a function of depth in the human cornea and limbus
Christina S. Kamma-Lorger Craig Boote Sally Hayes Julian Moger Manfred Burghammer Carlo Knupp Andrew J. Quantock Thomas Sorensen Emanuela Di Cola Nick White Robert D. Young Keith M. Meek 《Journal of structural biology》2010,169(3):424-430
A network of circumferentially oriented collagen fibrils exists in the periphery of the human cornea, and is thought to be pivotal in maintaining corneal biomechanical stability and curvature. However, it is unknown whether or not this key structural arrangement predominates throughout the entire corneal thickness or exists as a discrete feature at a particular tissue depth; or if it incorporates any elastic fibres and how, with respect to tissue depth, the circumcorneal annulus integrates with the orthogonally arranged collagen of the central cornea. To address these issues we performed a three-dimensional investigation of fibrous collagen and elastin architecture in the peripheral and central human cornea using synchrotron X-ray scattering and non-linear microscopy. This showed that the network of collagen fibrils circumscribing the human cornea is located in the posterior one-third of the tissue and is interlaced with significant numbers of mature elastic fibres which mirror the alignment of the collagen. The orthogonal arrangement of collagen in the central cornea is also mainly restricted to the posterior stromal layers. This information will aid the development of corneal biomechanical models aimed at explaining how normal corneal curvature is sustained and further predicting the outcome of surgical procedures. 相似文献
86.
87.
88.
Astrid Grottke Florian Ewald Tobias Lange Dominik N?rz Christiane Herzberger Johanna Bach Nicole Grabinski Lareen Gr?ser Frank H?ppner Bj?rn Nashan Udo Schumacher Manfred Jücker 《PloS one》2016,11(1)
Background
Treatment of breast cancer patients with distant metastases represents one of the biggest challenges in today’s gynecological oncology. Therefore, a better understanding of mechanisms promoting the development of metastases is of paramount importance. The serine/threonine kinase AKT was shown to drive cancer progression and metastasis. However, there is emerging data that single AKT isoforms (i.e. AKT1, AKT2 and AKT3) have different or even opposing functions in the regulation of cancer cell migration in vitro, giving rise to the hypothesis that inhibition of distinct AKT isoforms might have undesirable effects on cancer dissemination in vivo.Methods
The triple negative breast cancer cell line MDA-MB-231 was used to investigate the functional roles of AKT in migration and metastasis. AKT single and double knockdown cells were generated using isoform specific shRNAs. Migration was analyzed using live cell imaging, chemotaxis and transwell assays. The metastatic potential of AKT isoform knockdown cells was evaluated in a subcutaneous xenograft mouse model in vivo.Results
Depletion of AKT3, but not AKT1 or AKT2, resulted in increased migration in vitro. This effect was even more prominent in AKT2,3 double knockdown cells. Furthermore, combined downregulation of AKT2 and AKT3, as well as AKT1 and AKT3 significantly increased metastasis formation in vivo. Screening for promigratory proteins revealed that downregulation of AKT3 increases the expression of S100A4 protein. In accordance, depletion of S100A4 by siRNA approach reverses the increased migration induced by knockdown of AKT3.Conclusions
We demonstrated that knockdown of AKT3 can increase the metastatic potential of triple negative breast cancer cells. Therefore, our results provide a rationale for the development of AKT isoform specific inhibitors. 相似文献89.
Hieke M Greiner C Thieme TM Schubert-Zsilavecz M Werz O Zettl H 《Bioorganic & medicinal chemistry letters》2011,21(5):1329-1333
Dual inhibition of microsomal prostaglandin E2 synthase-1 (mPGES-1) and 5-lipoxygenase (5-LO) represents a promising strategy in the development of novel anti-inflammatory drugs targeting the arachidonic acid cascade. Herein, a class of α-naphthyl pirinixic acids is characterized as dual mPGES-1/5-LO inhibitors. Systematic structural variation was focused on the lipophilic backbone of the scaffold and yielded detailed structure-activity relationships (SAR) with compound 16 (IC50 mPGES-1 = 0.94 μM; IC50 5-LO = 0.1 μM) showing the most favorable in vitro pharmacological profile. 相似文献
90.
René H?hn Ulrike Kottler Tunde Peto Maria Blettner Thomas Münzel Stefan Blankenberg Karl J. Lackner Manfred Beutel Philipp S. Wild Norbert Pfeiffer 《PloS one》2015,10(3)