全文获取类型
收费全文 | 44470篇 |
免费 | 4160篇 |
国内免费 | 33篇 |
专业分类
48663篇 |
出版年
2022年 | 271篇 |
2021年 | 603篇 |
2020年 | 336篇 |
2019年 | 411篇 |
2018年 | 554篇 |
2017年 | 513篇 |
2016年 | 925篇 |
2015年 | 1593篇 |
2014年 | 1735篇 |
2013年 | 2204篇 |
2012年 | 2759篇 |
2011年 | 2839篇 |
2010年 | 1856篇 |
2009年 | 1792篇 |
2008年 | 2607篇 |
2007年 | 2622篇 |
2006年 | 2552篇 |
2005年 | 2520篇 |
2004年 | 2458篇 |
2003年 | 2418篇 |
2002年 | 2368篇 |
2001年 | 500篇 |
2000年 | 387篇 |
1999年 | 570篇 |
1998年 | 675篇 |
1997年 | 482篇 |
1996年 | 438篇 |
1995年 | 429篇 |
1994年 | 411篇 |
1993年 | 416篇 |
1992年 | 344篇 |
1991年 | 323篇 |
1990年 | 332篇 |
1989年 | 249篇 |
1988年 | 301篇 |
1987年 | 280篇 |
1986年 | 276篇 |
1985年 | 336篇 |
1984年 | 391篇 |
1983年 | 345篇 |
1982年 | 442篇 |
1981年 | 438篇 |
1980年 | 418篇 |
1979年 | 277篇 |
1978年 | 303篇 |
1977年 | 274篇 |
1976年 | 282篇 |
1975年 | 213篇 |
1974年 | 283篇 |
1973年 | 261篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
181.
Richard C. Woodman John T. Curnutte Bernard M. Babior 《Free radical biology & medicine》1988,5(5-6):355-361
We examined the effects of the recombinant human colony stimulating factors GM-CSF and G-CSF, cycloheximide (a protein synthesis inhibitor) and dihydrocytochalasin B (a microfilament disrupting agent) upon FMLP (N-formyl-methionyl-leucylphenylalanine)-stimulated O2 − production by neutrophils. We confirmed a time dependent augmentation of O2 − production following preincubation of neutrophils either alone or with colony stimulating factors. Furthermore, we found that GM-CSF, but not G-CSF, increased O2 − production at some concentrations of the stimulus. Preincubation of neutrophils with cycloheximide in the absence of CSF caused a marked fall in O2−-production that was first evident at 2 hours. The fall in O2−-forming capacity caused by cycloheximide was much less pronounced if dihydrocytochalasin B was also included in the preincubation buffer. These findings suggest a previously unrecognized role for de novo protein synthesis in maintaining the ability of neutrophils to manufacture O2−, and support earlier studies indicating that the cycling of FMLP receptors between the cell membrane and an intracellular compartment is important in determining the magnitude of the respiratory burst in FMLP-stimulated neutrophils. 相似文献
182.
Neurotransmitter receptors and ion channels play a critical role in the transduction of signals at chemical synapses. The modulation of neurotransmitter receptor and ion channel function by protein phosphorylation is one of the major regulatory mechanisms in the control of synaptic transmission. The nicotinic acetylcholine receptor (nAcChR) has provided an excellent model system in which to study the modulation of neurotransmitter receptors and ion channels by protein phosphorylation since the structure and function of this receptor have been so extensively characterized. In this article, the structure of the nAcChR from the electric organ of electric fish, skeletal muscle, and the central and peripheral nervous system will be briefly reviewed. Emphasis will be placed on the regulation of the phosphorylation of nAcChR by second messengers and by neurotransmitters and hormones. In addition, recent studies on the functional modulation of nicotinic receptors by protein phosphorylation will be reviewed. 相似文献
183.
184.
185.
Improved media for normal human muscle satellite cells: Serum-free clonal growth and enhanced growth with low serum 总被引:5,自引:0,他引:5
Richard G. Ham Judy A. St. Clair Cecelia Webster Helen M. Blau 《In vitro cellular & developmental biology. Plant》1988,24(8):833-844
Summary We have developed a serum-free medium for clonal growth of normal human muscle satellite cells (HMSC). It consists of an optimized
nutrient medium MCDB 120, plus a serum-free supplement, designated SF, that contains epidermal growth factor (EGF), insulin,
dexamethasone, bovine serum albumin, and fetuin. Fibroblast growth factor was needed with dialyzed fetal bovine serum (dFBS)
as the only other supplement, but in media containing SF, it was only slightly beneficial, and was omitted from the final
medium without significant loss. Clonal growth of HMSC in MCDB 120 plus SF is as good as with 15% serum and 0.5% chicken embryo
or bovine pituitary extract. However, growth is further improved by use of a doubly-supplemented (DS) medium containing both
SF and 5% dFBS. Clonal growth of HMSC in the DS medium far exceeds that in previous media with any amount of serum, and monolayer
growth is at least equal to that in conventional media with higher levels of serum. Cells grown in these media exhibit little
differentiation, even when grown to high densities. However, they retain the capacity for extensive fusion and synthesis of
increased creatine kinase when transferred to a serum-free differentiation-promoting medium, such as Dulbecco's modified Eagle's
medium plus insulin. All experiments were done with clonal cultures of HMSC to insure that observed growth responses were
always those of muscle cells.
This research was supported by a grant from the Muscular, Dystrophy Association.
Editor's statement This article describes the optimization of both the basal nutrient medium and growth factor requirements
for human muscle cells in vitro. This system is critical for studies of normal muscle cell and molecular biology, as well
as for understanding diseases of muscle such as Duchenne, Muscular Dystrophy. 相似文献
186.
Allison A. Welder Tina Machu Steven W. Leslie Richard E. Wilcox June Bradlaw Daniel Acosta 《In vitro cellular & developmental biology. Plant》1988,24(8):771-777
Summary Primary mycolardial cell cultures and freshly isolated cardiac cells in suspension resprensent two isolated, whole cell models
for investigating cellular transsarcolemmal45Ca++ exchange in response to a receptor-coupled stimulus. Studies were performed to characterize beta-adrenergic receptor binding,
beta-adrenergic receptor mediated cellular calcium (45Ca++) exchange, and viability in purified primary myocardial cell cultures and freshly isolated cardiac cells in suspension obtained
from 3-to 3-d-old Sprague-Dawley rats. In addition, beta-adrenergic receptor binding was characterized in whole-heart crude
membrane preparations. All three preparations had saturable beta-adrenergic binding sites with the antagonist [125I]iodopindolol ([125I]IPIN). The suspensions had a significantly lower B
max
(42±6 fmol/mg protein) than the membranes and cultures (77±8 and 95±10 fmol/mg protein, respectively). The K
D
of the cultures (218±2.0 pM) was significantly higher than that for the suspensions (107 ±1.3 pM) and membranes (93±1.3 pM). Viability was significantly lower in the suspensions (57%) when compared to 94% viability in myocardial cell cultures after
3 h of incubation in Kreb's Henseleit buffer. Incubation of the cultures with 5.0×10−7
M isoproterenol resulted in a significant increase in45Ca++ exchange as early as 15 s. In contrast,45Ca++ exchange into the suspensions was not increased. Although both primary cell cultures and cardiac cells in suspension possess
saturable beta-adrenergic receptors, only the monolayer cultures exhibited functional beta-adrenergic receptor-mediated45Ca++ exchange. Of the two intact cell models investigated, these data suggest that primary myocardial cell cultures are more suitable
than cell suspensions for investigating beta-adrenergic receptor binding and functions in the postnatal rat heart.
This research was supported by The University of Texas Research Institute, a grant from the Texas Advanced Research Technology
Program awarded to S. W. Leslie and R. E. Wilcox, and contract 223-86-2109 from the Food and Drug Administration. 相似文献
187.
Richard B. King 《Evolutionary ecology》1992,6(2):115-124
Summary Populations of water snakes (Nerodia sipedon insularum) on islands in western Lake Erie are variable in colour pattern, consisting of unbanded, intermediate, and banded morphs. In contrast, mainland populations (N. s. sipedon) consist solely of banded morphs. Previous investigators hypothesized that natural selection favoured unbanded morphs on exposed island shorelines and banded morphs in overgrown mainland habitats and that gene flow from mainland populations was responsible for the persistence of banded morphs on islands. To clarify the potential role of natural selection, I quantified relative crypsis among morphs and age classes of water snakes by comparing the size of patches making up their colour patterns with the size of patches in island and mainland backgrounds. This analysis reveals that if unbanded morphs are more cryptic than intermediate and banded morphs on islands, it is only in the young-of-the-year age class. For older snakes on islands and for all snakes on the mainland, unbanded morphs are consistently less cryptic than intermediate and banded morphs. Given these results, the net direction of selection in island populations should depend on the intensity of predation on different age classes of snakes. Overall, selection may favour unbanded morphs (e.g. if predation occurs primarily on young-of-the-year), intermediate and banded morphs (e.g. if predation occurs primarily on older snakes), or be weak or absent (e.g. certain combinations of predation on young-of-the-year and older snakes). Using estimates of relative crypsis to guide reanalysis of morph frequency data, I find support for the hypothesis that unbanded morphs are favoured by natural selection in island populations. 相似文献
188.
David K. Grandy Richard Leduc Haripriya Makam Thomas Flanagan Emanuel J. Diliberto Jr. Olivier Civelli O. Humberto Viveros 《Cellular and molecular neurobiology》1992,12(2):185-192
1. A novel 1745-dalton pyroglutamyl peptide (BAM-1745)6 was recently isolated and characterized from bovine adrenal medulla chromaffin granules. Its amino acid sequence was found to be 93% identical to residues 580-593 of human chromogranin B (secretogranin I). 2. Based on this sequence a degenerate oligonucleotide probe was synthesized and used to identify a 2.4-kb bovine adrenal medulla chromogranin B cDNA. 3. The deduced polypeptide is 647 amino acids long and begins with a putative signal sequence of 20 residues as in the human, rat, and mouse proteins. Also conserved in the bovine protein is a tyrosine residue which may be sulfated, two N-terminal cysteines, and many paired basic amino acids which may serve as sites of posttranslational processing. The peptide BAM-1745 is flanked by paired basic amino acids and therefore is most likely a product of posttranslational processing. Bovine chromogranin B is 67, 58, and 58% identical to the human, rat, and mouse chromogranin B proteins, respectively. 4. The carboxyl terminus of bovine chromogranin B, including BAM-1745, was found to be the most conserved region of the polypeptide and may identify it as an important functional domain. 相似文献
189.
Summary Aberrations of photoreceptor ultrastructure resulting from carotenoid/retinoid (vitamin A) deprivation were studied in the retina of Manduca sexta. The syndrome of chromophore deficiency included hypertrophy of smooth endoplasmic reticulum, variable dilation of rhabdomeric microvilli, the insertion of endomembrane fingers into such enlarged microvilli, and the formation of rhabdomeric vacuoles, intracellular compartments containing microvilli similar to those of the rhabdomere. Retinas were processed either with conventional procedures employing preliminary aldehyde fixation followed by heavy metal postfixation, or by fixation and incubation in unbuffered OsO4. The latter method deposits osmium throughout the endomembrane system, within the rhabdomeric vacuoles, and in the extracellular space of the rhabdom. However, the intravillous fingers were rarely impregnated with osmium, despite their continuity with densely stained cisternae of the smooth endoplasmic reticulum. We suggest that the insertion of endomembrane fingers into dilated microvilli results from a cytoskeleton-mediated link between cisternae of the smooth endoplasmic reticulum and the rhabdomeric membrane, an association that may be important in the turnover of photoreceptor membrane. We interpret endomembrane hypertrophy and development of rhabdomeric vacuoles as symptoms of disturbance in the pathway leading to the assembly of the rhabdomere resulting from reduced synthesis of visual pigment. 相似文献
190.
Dipak K. Das Richard M. Engelman Xuekun Liu Swapna Maity John A. Rousou Joseph Flack Jitendra Laksmipati Randall M. Jones M. Renuka Prasad David W. Deaton 《Molecular and cellular biochemistry》1992,111(1-2):77-86
Reperfusion injury occurs during open-heart surgery after prolonged cardioplegic arrest. Cardiopulmonary bypass also is known to cause hemolysis. Since reperfusion of ischemic myocardium is associated with the generation of oxygen free radicals, and since free radicals can attack a protein molecule, it seems reasonable to assume that hemolysis might be the consequence of free radical attack on hemoglobin protein. The results of this study demonstrated that reperfusion following ischemic arrest caused an increase in free hemoglobin and free heme concentrations, simultaneously releasing free iron and generating hydroxyl radicals. In vitro studies using pure hemoglobin indicated that superoxide anion generated by the action of xanthine oxidase on xanthine could release iron from the heme ring and cause deoxygenation of oxyhemoglobin into ferrihemoglobin. This study further demonstrated that before the release of iron from the heme nucleus, oxyhemoglobin underwent deoxygenation to ferrihemoglobin. The released iron can catalyze the Fenton reaction, leading to the formation of cytotoxic hydroxyl radical (OH·). In fact, the formation of OH. in conjunction with hemolysis occurs during cardiac surgery, and when viewed in the light of the in vitro results, it seems likely that oxygen-derived free radicals may cause hemolysis during cardiopulmonary bypass and simultaneously release iron from the heme ring, which can catalyze the formation of OH·. 相似文献