全文获取类型
收费全文 | 4587篇 |
免费 | 362篇 |
国内免费 | 1篇 |
出版年
2023年 | 25篇 |
2022年 | 31篇 |
2021年 | 100篇 |
2020年 | 80篇 |
2019年 | 94篇 |
2018年 | 109篇 |
2017年 | 102篇 |
2016年 | 155篇 |
2015年 | 202篇 |
2014年 | 247篇 |
2013年 | 303篇 |
2012年 | 341篇 |
2011年 | 321篇 |
2010年 | 178篇 |
2009年 | 214篇 |
2008年 | 250篇 |
2007年 | 245篇 |
2006年 | 249篇 |
2005年 | 214篇 |
2004年 | 216篇 |
2003年 | 199篇 |
2002年 | 190篇 |
2001年 | 52篇 |
2000年 | 48篇 |
1999年 | 66篇 |
1998年 | 51篇 |
1997年 | 40篇 |
1996年 | 36篇 |
1995年 | 38篇 |
1994年 | 28篇 |
1993年 | 38篇 |
1992年 | 34篇 |
1991年 | 30篇 |
1990年 | 42篇 |
1989年 | 43篇 |
1988年 | 31篇 |
1987年 | 26篇 |
1986年 | 21篇 |
1985年 | 21篇 |
1984年 | 15篇 |
1983年 | 17篇 |
1982年 | 30篇 |
1981年 | 16篇 |
1980年 | 28篇 |
1979年 | 13篇 |
1978年 | 11篇 |
1977年 | 13篇 |
1976年 | 9篇 |
1975年 | 12篇 |
1973年 | 17篇 |
排序方式: 共有4950条查询结果,搜索用时 15 毫秒
81.
During the night anchovies were observed in the deep offshore oceanic and intermediate slope zones off the Baja California coast, Mexico, in high abundance. Anchovies moved towards the shallow inshore neritic zone in low density groups, returning at dawn to deeper depth strata. During the day, abundances were reduced drastically and those observed were forming compact and discrete schools at deeper depth strata. Anchovy and euphausiid abundance, as recorded by the echosounder, Were positively correlated. 相似文献
82.
Michael J. Seckl Richard H. Newman Paul S. Freemont Enrique Rozengurt 《Journal of cellular physiology》1995,163(1):87-95
The substance P (SP) analogues [DArg1, DPhe5, DTrp7,9, Leu11] SP (AntD) and [Arg6, DTrp7,9, MePhe8] SP (6–11) (AntG) inhibit the action of many different neuropeptides including SP. These analogues might be useful in the treatment of small cell lung cancer but their mechanism of action is unclear. Here, we analyzed the effect of AntD and AntG on neuropeptide vs. guanosine 5′-3-O-(thio) triphosphate (GTPγS) stimulated inositol phosphate generation in permeabilized Swiss 3T3 cells. AntD inhibited vasopressin and bombesin stimulated inositol phosphate formation (IC50 of 0.75 μM and 2 μM, respectively). Similarly, AntG inhibited vasopressin-stimulated inositol phosphate generation with an IC50 of 1 μM. Strikingly, neither AntD up to 10 μM nor AntG up to 20 μM was able to inhibit GTPγS-stimulated inositol phosphate generation. Dose-response curves of neuropeptide-induced inositol phosphate generation were dramatically displaced to the right by either 10 μM AntD or 20 μM AntG. However, neither antagonist affected the dose response of GTPγS-stimulated inositol phosphate generation. Furthermore, 20 μM AntD had no effect on AIF?4-induced inositol phosphates in COS-1 cells transfected with Gαq. AntD inhibited [3H]vasopressin binding competitively in intact Swiss 3T3 cells and both AntD and AntG inhibited [3H]vasopressin binding in Swiss 3T3 and rat liver membranes. Scatchard analysis revealed that AntD inhibited vasopressin binding by reducing receptor affinity without affecting receptor number in both intact and membrane preparations of Swiss 3T3 cells. The results strongly suggest that SP analogues AntD and AntG block the action of the Ca2+ mobilizing neuropeptides at the receptor level, rather than inhibiting G protein-stimulated inositol phosphate production. © 1995 Wiley-Liss, Inc. 相似文献
83.
Marcela B. Ortiz Mercedes Goin Maria B. Gomez de Alzaga Swen Hammarstrom Luis Jimenez de Asua 《Journal of cellular physiology》1995,162(1):139-146
Lovastatin (LOV), a hydroxy-methylglutaryl-coenzyme A (HMGCoA) reductase competitive inhibitor, blocks epidermal growth factor (EGF)— or prostaglandin F2α (PGF2α)—induced mitogenesis in confluent resting Swiss 3T3 cells. This inhibition occurs even in the presence of insulin, which potentiates the action of these mitogens in such cells. LOV exerts its effect in a 2–80 μM concentration range, with both mitogens attaining 50% inhibition at 7.5 μM. LOV exerted its effect within 0–8 h following mitogenic induction. Mevanolactone (10–80 μM) in the presence of LOV could reverse LOV inhibition within a similar time period. LOV-induced blockage of PGF2α response is reflected in a decrease in the rate of cell entry into S phase. Neither cholesterol, ubiquinone, nor dolichols of various lengths could revert LOV blockage. In EGF- or PGF2α-stimulated cells, LOV did not inhibit [3H]leucine or [3H]mannose incorporation into proteins, while tunicamycin, an inhibitor of N′ glycosylation, prevented this last phenomenon. Thus, it appears that LOV exerts its action neither by inhibiting unspecific protein synthesis nor by impairing the N′ glycosylation process. These findings strongly suggest that either EGF or PGF2α stimulations generate early cell cycle signals which induce mevalonate formation, N′ glycoprotein synthesis, and proliferation. The causal relationship of these events to various mechanisms controlling the onset of DNA synthesis is also discussed. © 1995 Wiley-Liss, Inc. 相似文献
84.
Abstract: Different neurotransmitter receptor agonists [carbachol, serotonin, noradrenaline, histamine, endothelin-1, and trans -(1 S ,3 R )-aminocyclopentyl-1,3-dicarboxylic acid ( trans -ACPD)], known as stimuli of phospholipase C in brain tissue, were tested for phospholipase D stimulation in [32 P]Pi -prelabeled rat brain cortical and hippocampal slices. The accumulation of [32 P]phosphatidylethanol was measured as an index of phospholipase D-catalyzed transphosphatidylation in the presence of ethanol. Among the six neurotransmitter receptor agonists tested, only noradrenaline, histamine, endothelin-1, and trans -ACPD stimulated phospholipase D in hippocampus and cortex, an effect that was strictly dependent of the presence of millimolar extracellular calcium concentrations. The effect of histamine (EC50 18 µ M ) was inhibited by the H1 receptor antagonist mepyramine with a K i constant of 0.7 n M and was resistant to H2 and H3 receptor antagonists (ranitidine and tioperamide, respectively). Endothelin-1-stimulated phospholipase D (EC50 44 n M ) was not blocked by BQ-123, a specific antagonist of the ETA receptor. Endothelin-3 and the specific ETB receptor agonist safarotoxin 6c were also able to stimulate phospholipase D with efficacies similar to that of endothelin-1, and EC50 values of 16 and 3 n M , respectively. These results show that histamine and endothelin-1 stimulate phospholipase D in rat brain through H1 and ETB receptors, respectively. 相似文献
85.
Jesús Mateo Enrique Castro Jean Zwiller Dominique Aunis M. T. Miras-Portugal 《Journal of neurochemistry》1995,64(1):77-84
Abstract: We investigated the effect of the adenosine receptor agonist 5'-( N -ethylcarboxamido)adenosine (NECA) in catecholamine secretion from adrenal chromaffin cells that exhibit only the A2b subtype adenosine receptor. NECA reduced catecholamine release evoked by the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP) in a time-dependent manner. Inhibition reached 25% after 30–40-min exposure to NECA. This effect on DMPP-evoked catecholamine secretion was mirrored by a similar (27.7 ± 3.3%), slowly developing inhibition of [Ca2+ ]i transients induced by DMPP that peaked at 30-min preincubation with NECA. The capacity of the chromaffin cells to buffer Ca2+ load was not affected by the treatment with NECA. Short-term treatment with NECA failed both to modify [Ca2+ ]i levels and to increase endogenous diacylglycerol production, showing that NECA does not activate the intracellular Ca2+ /protein kinase C signaling pathway. The inhibitory effects of NECA were accompanied by a 30% increase of protein phosphatase activity in chromaffin cell cytosol. We suggest that dephosphorylation of a protein involved in DMPP-evoked Ca2+ influx pathway (e.g., L-type Ca2+ channels) could be the mechanism of the inhibitory action of adenosine receptor stimulation on catecholamine secretion from adrenal chromaffin cells. 相似文献
86.
Toxicology of vanadium compounds in diabetic rats: The action of chelating agents on vanadium accumulation 总被引:1,自引:0,他引:1
Jose L. Domingo Mercedes Gomez Domenec J. Sanchez Juan M. Llobet Carl L. Keen 《Molecular and cellular biochemistry》1995,153(1-2):233-240
The possible use of vanadium compounds in the treatment of diabetic patients is now being evaluated. However, previously to establish the optimal maximum dose for diabetes therapy, it should be taken into account that vanadium is a highly toxic element to man and animals. The toxic effects of vanadium are here reviewed. The tissue vanadium accumulation, which would mean an additional risk of toxicity following prolonged vanadium administration is also discussed. Recently, it has been shown that coadministration of vanadate and TIRON, an effective chelator in the treatment of vanadium intoxication, reduced the tissue accumulation of this element, decreasing the possibility of toxic side effects derived from chronic vanadium administration without diminishing the hypoglycemic effect of vanadium. However, previously to assess the effectiveness of this treatment in diabetic patients, a critical reevaluation of the antidiabetic action of vanadium and its potential toxicity is clearly needed. 相似文献
87.
Ruth Meléndez Enrique Meléndez-Hevia Marta Cascante 《Journal of molecular evolution》1997,45(4):446-455
Optimization of molecular design in cellular metabolism is a necessary condition for guaranteeing a good structure–function
relationship. We have studied this feature in the design of glycogen by means of the mathematical model previously presented
that describes glycogen structure and its optimization function [Meléndez-Hevia et al. (1993), Biochem J 295: 477–483]. Our
results demonstrate that the structure of cellular glycogen is in good agreement with these principles. Because the stored
glucose in glycogen must be ready to be used at any phase of its synthesis or degradation, the full optimization of glycogen
structure must also imply the optimization of every intermediate stage in its formation. This case can be viewed as a molecular
instance of the eye problem, a classical paradigm of natural selection which states that every step in the evolutionary formation of a functional structure
must be functional. The glycogen molecule has a highly optimized structure for its metabolic function, but the optimization
of the full molecule has meaning and can be understood only by taking into account the optimization of each intermediate stage
in its formation.
Received: 23 October 1996 / Accepted: 21 April 1997 相似文献
88.
Enrique A. Gonzlez Froiln Vzquez Jos Ignacio Garabal Jorge Blanco 《Microbiology and immunology》1995,39(12):937-942
Fimbriae isolation by means of thermal shock was applied to fifteen K88-positive (three K88ab, nine K88ac and three K88ad) Escherichia coli reference strains belonging to serotypes O8:K87, O32, O45, O138:K81, O141:K85, O147:K89, O149:K91, and O157, as well as to ten K88-positive enterotoxigenic strains isolated from porcine diarrhea in Spain, all of them belonging to the O149 serogroup. Fimbriae were removed from the bacterial cells by thermal shock at 60 C and then precipitated using ammonium sulfate. The final amount of K88 antigen and the purification degree were not related to the serogroup of the bacteria or to the antigen variant but were related to the buffer used for isolation. Phosphate buffer containing urea was shown to be more effective than Tris-HCl for isolation of K88 antigen. The molecular weights by SDS-PAGE for K88ab, K88ac, and K88ad were 28.5, 29.2, and 31.0 kDa, respectively. All enterotoxigenic E. coli strains isolated in Spain showed the K88ac variant. 相似文献
89.
André Breton Brigitte Gaillard-Martine Corinne Gerbi Béatrice Gomez de Ségura Roger Durand Belgacem Kherratia 《Current microbiology》1995,31(4):224-227
-d-Glucosidase, -d-fucosidase -d-xylosidase, and -cellobiopyranosidase activities in Caecomyces communis, Neocallimastix frontalis, and Piromyces rhizinflata, located with fluorescent conjugates, occur throughout the whole thallus as from zoospore germination and disappear before sporulation. -d-Galactosidase and -l-arabinopyranosidase activities are low or nonexistent. A xylanase, detected by indirect immunofluorescence, was observed at the surface of the vegetative cells, vesicles, or rhizoids. Cross-reactions prove the existence of analogies in structure among the enzymes of these anaerobic gut fungi. 相似文献
90.
Location of the active site of the bean {alpha}-amylase inhibitor and involvement of a Trp, Arg, Tyr triad 总被引:1,自引:0,他引:1
Mirkov T.Erik; Evans Stephen V.; Washlstrom Janice; Gomez Luis; Young N.Martin; Chrispeels Maarten J. 《Glycobiology》1995,5(1):45-50
Seeds of the common bean contain three homologous proteins:phytohaemagglutinin E, phytohaemagglutinin L and the lectin-likeprotein 相似文献