全文获取类型
收费全文 | 4336篇 |
免费 | 314篇 |
国内免费 | 1篇 |
专业分类
4651篇 |
出版年
2023年 | 18篇 |
2022年 | 39篇 |
2021年 | 106篇 |
2020年 | 63篇 |
2019年 | 81篇 |
2018年 | 107篇 |
2017年 | 91篇 |
2016年 | 145篇 |
2015年 | 193篇 |
2014年 | 225篇 |
2013年 | 259篇 |
2012年 | 403篇 |
2011年 | 354篇 |
2010年 | 234篇 |
2009年 | 176篇 |
2008年 | 259篇 |
2007年 | 274篇 |
2006年 | 270篇 |
2005年 | 197篇 |
2004年 | 225篇 |
2003年 | 207篇 |
2002年 | 189篇 |
2001年 | 33篇 |
2000年 | 30篇 |
1999年 | 46篇 |
1998年 | 54篇 |
1997年 | 44篇 |
1996年 | 29篇 |
1995年 | 41篇 |
1994年 | 25篇 |
1993年 | 17篇 |
1992年 | 22篇 |
1991年 | 22篇 |
1990年 | 28篇 |
1989年 | 13篇 |
1988年 | 16篇 |
1987年 | 11篇 |
1986年 | 9篇 |
1985年 | 8篇 |
1984年 | 9篇 |
1983年 | 13篇 |
1982年 | 3篇 |
1981年 | 12篇 |
1980年 | 8篇 |
1979年 | 6篇 |
1978年 | 6篇 |
1977年 | 7篇 |
1975年 | 12篇 |
1973年 | 4篇 |
1972年 | 2篇 |
排序方式: 共有4651条查询结果,搜索用时 15 毫秒
11.
Study of the in vitro bioactivation of albendazole in human liver microsomes and hepatoma cell lines
Sylvie Rolin Hajar Souhaili-El Amri Anne-Marie Batt Michele Levy Denyse Bagrel Gerard Siest 《Cell biology and toxicology》1989,5(1):1-14
The metabolism of albendazole (ABZ), a benzimidazole anthelminthic, was studied in either microsomal preparations of human liver biopsies or cultured human hepatoma cell lines. Metabolites were analyzed by HPLC. Our data show that microsomes from human biopsies and two human cell lines, HepG2 and Hep3B, oxidize the drug to the sulfoxide very efficiently, whereas the third cell line tested, SK-HEP-1, does not. Both cytochrome P-450 dependent monooxygenases and favin-containing monooxygenases appear to be involved in human ABZ metabolism. Using the cell line displaying the highest ABZ-metabolizing activity, HepG2, the cytotoxic and the inducing effects of the parent drug ABZ and of two primary metabolites, the sulfoxide and the sulfone were studied. These three chemicals provoked a rise in mitotic index resulting from cell division blockage at the prophase or at the metaphase (ABZ metabolites) stage, and ABZ was more cytotoxic than its metabolites. With regard to enzyme-inducing effects, our data clearly demonstrate that the sulfoxide and, to a lesser degree, the sulfone are potent inducers of some drug metabolizing enzymes (i.e., cytochrome P-488 dependent monooxygenases and UDP glucuronyltransferase), whereas ABZ fails to increase and even slightly decreases these enzymatic activities. In conclusion, the HepG2 human hepatoma cell line appears to be suitable for the study of many parameters of metabolism and action of ABZ and other structurally related compounds in humans.Abbreviations ABZ
albendazole
- B[a]P
benzo[a]pyrene
- HPLC
high-performance liquid chromatography
- MC
3-methylcholanthrene
- MFO
mixed-function oxidase
- UDPGT
UDP-glucuronyltransferase 相似文献
12.
Summary Inward-rectifier channels in cardiac cells (I
K1) stabilize the resting membrane potential near the K equilibrium potential. Here we investigate the role ofI
K1 in the regulation of action potentials and link this to the influx of Ca during beating. Inward Ca current alters the open-channel probability of outwardI
K1 current. Thus Ca ions depolarize cells not only by carrying an inward current but also by blocking an outward current. 相似文献
13.
Summary The role of tubular mastigonemes in the reversal of thrust of the anterior flagellum ofPhytophthora cinnamomi was analysed using mastigoneme-specific monoclonal antibodies and immunoflu-orescence and video microscopy. Exposure of live zoospores ofP. cinnamomi to the mastigoneme-specific Zg antibodies caused alterations in the arrangement of mastigonemes on the flagellar surface and at Zg concentrations above 0.3 /ml, mastigonemes became detached from the flagellum. As a consequence of antibody binding to the mastigonemes there were concentration-dependent perturbations in zoospore swimming behaviour and anterior flagellum beat pattern. With increasing antibody concentration zoospores swam more slowly and other parameters of their swimming pattern, such as the wavelength of the swimming helix and the frequency of rotation, were also reduced. The effects of Zg antibodies were specific at two levels: control immunoglobulins or antibodies that bound to other flagellar surface components did not have an effect on motility, and Zg antibodies did not interfere with the motility of zoospores of oomycete species to which they did not bind. The effects of antibody-induced disruption of mastigoneme arrangement strongly support previous hypotheses that tubular mastigonemes are responsible for thrust reversal by the anterior flagellum, enabling it to pull the cell through the surrounding medium. 相似文献
14.
David W. Inouye Douglas E. Gill Michele R. Dudash Charles B. Fenster 《American journal of botany》1994,81(12):1517-1530
As pollination biology undergoes unprecedented growth as a discipline, confusion in the use of terms has become increasingly common. The need for a flexible yet unambiguous terminology has become urgent. As an example we discuss how the term “pollination efficiency” is used differently by 18 studies, and “pollinator effectiveness” by seven others. Here we present flowcharts of two general models of pollination systems (biotic and abiotic) that trace all the events from pollen production to development of seed or fruit, and we develop a lexicon for the quantities of pollen, processes of transfers (to a vector, to a stigma), and ratios of quantities that are of interest in studies of pollination and mating systems. An appendix includes a glossary of the definitions we suggest. 相似文献
15.
Identification of a nucleo-cytoplasmic ionic pathway by osmotic shock in isolated mouse liver nuclei
Summary The observation that the nuclear envelope outer mem brane contains ion channels raises the question of whether these conductances
communicate between the cytosol and the nuclear envelope cisternae or between the cytosol and the cytoplasm. Failure to detect
large, nonselective holes using the patch-clamp technique has led to the speculation that ion channels and nuclear pores are
in fact the same.
In this paper we present evidence that the ionic channel, recorded in isolated liver nuclei with the patch-clamp configura
tion of “nucleus-attached,” spans the double membrane of the envelope, providing a direct contact between nucleoplasm and
cytoplasm. 相似文献
16.
Davide Barberis Giampiero Lombardi Simone Ravetto Enri Marco Pittarello Davide Viglietti Michele Freppaz Michele Lonati 《Restoration Ecology》2023,31(1):e13777
Machine grading is frequently required to prepare the terrain when building high-altitude ski slopes in the Alps. However, this kind of disturbance alters the natural environment, destroying the vegetation and hampering its reestablishment. Thus, specific restoration plans are necessary to encourage the recovery of vegetation, which is already affected by different natural constraints in this harsh environment. One of the main critical factors affecting plant growth in high-altitude areas is the lack of available nitrogen (N) in the soil. In this context, the addition of a slow-release N fertilizer was carried out in an experimental revegetated ski slope between 2,800 and 2,900 m above sea level in the western Italian Alps. Both vegetation and soil were monitored during a 5-year period in order to test the effectiveness of N addition on the restoration process. Even if effects on soil carbon and N contents were negligible, vegetation was remarkably affected by the fertilization, since the total vegetation cover and the species richness significantly increased. Against the expectations, there was a remarkable increase in spontaneous forbs, rather than in most of the sown graminoids, which slightly varied during the experimental period. Actually, graminoids responded in different ways, mostly increasing (likewise forbs), but the slight decrease of the dominant Festuca nigrescens (Chewing's Fescue) masked their spread. This study confirms the noteworthy role of N in high-altitude alpine soils and consequently its importance to improve the restoration process of degraded ecosystems. 相似文献
17.
Richard Swartz Loyd West Iouri Boiko Anais Malpica Calum MacAulay Anita Carraro Martial Guillaud Dennis Cox Michele Follen 《Analytical cellular pathology》2003,25(4):193-200
This is a methodological study exploring the use of quantitative histopathology applied to the cervix to discriminate between normal and cancerous (consisting of adenocarcinoma and adenocarcinoma in situ) tissue samples. The goal is classifying tissue samples, which are populations of cells, from measurements on the cells. Our method uses one particular feature, the IODs-Index, to create a tissue level feature. The specific goal of this study is to find a threshold for the IODs-Index that is used to create the tissue level feature. The main statistical tool is Receiver Operating Characteristic (ROC) curve analysis. When applied to the data, our method achieved promising results with good estimated sensitivity and specificity for our data set. The optimal threshold for the IODs-Index was found to be 2.12. 相似文献
18.
Vittorio Moretto Fernando Formaggio Marco Crisma Gian Maria Bonora Claudio Toniolo Ettore Benedetti Antonello Santini Michele Saviano Benedetto Di Blasio Carlo Pedone 《Journal of peptide science》1996,2(1):14-27
A complete series of terminally blocked, monodispersed homo-oligopeptides (to the pentamer level) from the sterically demanding, medium-ring alicyclic Cα,α-disubstituted glycine 1-aminocyclooctane-1-carb oxylic acid (Ac8c), and two Ala/Ac8c tripeptides, were synthesized by solution methods and fully characterized. The preferred conformation of all the oligopeptides was determined in deuterochloroform solution by IR absorption and 1H-NMR. The molecular structures of the amino acid derivative Z-Ac8c-OH, the dipeptide pBrBz- (Ac8c)2-OH and the tripeptide pBrBz-(Ac8c)3-OtBu were assessed in the crystal state by X-ray diffraction. Conformational energy computations were performed on the monopeptide Ac-Ac8c-NHMe. Taken together, the results obtained strongly support the view that the Ac8c residue is an effective β-turn and helix former. A comparison is also made with the conformational preferences of α-aminoisobutyric acid, the prototype of Cα, α-disubstituted glycines, and of the other members of the family of 1-aminocycloalkane-1-carboxylic acids (Acnc, with n=3, 5–7) investigated so far. The implications for the use of the Ac8c residue in peptide conformational design are considered. 相似文献
19.
This study addresses the ability of DNA fragments from various sources to mediate autonomous DNA replication in cultured Drosophila melanogaster cells. We created a series of plasmids containing genomic DNA fragments from the Ultrabithorax gene of Drosophila and tested them for autonomous replication after transfection into Schneider line 2 cells. We found that all plasmids containing Drosophila DNA fragments were able to replicate autonomously, as were plasmids containing random human and Escherichia coli genomic DNA fragments. Most of the plasmids were detectable 18 days after transfection in the absence of selection, suggesting that transfected DNA is maintained in Drosophila cells without rapid loss or degradation. The finding that all plasmids containing Drosophila, human, or bacterial DNA replicate autonomously in Drosophila cells suggests that the signals that direct autonomous replication in Drosophila contain a low degree of sequence specificity. A two-dimensional gel analysis of initiation on one of the plasmids was consistent with many dispersed initiation sites. Low sequence specificity and dispersed initiation sites also characterize autonomous replication in human cells and Senopus eggs and may be general properties of autonomous replication in animal cells. 相似文献
20.
Richard Cooke Monique Raynal Michele Laudié Michel Delseny 《The Plant journal : for cell and molecular biology》1997,11(5):1127-1140
Partial cDNA sequencing to obtain expressed sequence tags (ESTs) has led to the identification of tags to about 8000 of the estimated 20 000 genes in Arabidopsis thaliana . This figure represents four to five times the number of complete coding sequences from this organism available in international databases. In contrast to mammals, many proteins are encoded by multigene families in A. thaliana . Using ribosomal protein gene families as an example, it is possible to construct relatively long sequences from overlapping ESTs which are of sufficiently high quality to be able to unambiguously identify tags to individual members of multigene families, even when the sequences are highly conserved. A total of 106 genes encoding 50 different cytoplasmic ribosomal protein types have been identified, most proteins being encoded by at least two and up to four genes. Coding sequences of members of individual gene families are almost always very highly conserved and derived amino acid sequences are almost, if not completely, identical in the vast majority of cases. Sequence divergence is observed in untranslated regions which allows the definition of gene-specific probes. The method can be used to construct high-quality tags to any protein. 相似文献