全文获取类型
收费全文 | 12079篇 |
免费 | 1504篇 |
国内免费 | 3篇 |
专业分类
13586篇 |
出版年
2021年 | 177篇 |
2019年 | 122篇 |
2018年 | 137篇 |
2017年 | 130篇 |
2016年 | 227篇 |
2015年 | 357篇 |
2014年 | 364篇 |
2013年 | 472篇 |
2012年 | 585篇 |
2011年 | 545篇 |
2010年 | 370篇 |
2009年 | 335篇 |
2008年 | 448篇 |
2007年 | 426篇 |
2006年 | 427篇 |
2005年 | 414篇 |
2004年 | 389篇 |
2003年 | 394篇 |
2002年 | 375篇 |
2001年 | 364篇 |
2000年 | 380篇 |
1999年 | 330篇 |
1998年 | 165篇 |
1997年 | 179篇 |
1996年 | 178篇 |
1995年 | 126篇 |
1994年 | 139篇 |
1993年 | 139篇 |
1992年 | 265篇 |
1991年 | 242篇 |
1990年 | 248篇 |
1989年 | 231篇 |
1988年 | 220篇 |
1987年 | 219篇 |
1986年 | 176篇 |
1985年 | 224篇 |
1984年 | 175篇 |
1983年 | 149篇 |
1982年 | 155篇 |
1981年 | 140篇 |
1980年 | 117篇 |
1979年 | 171篇 |
1978年 | 138篇 |
1977年 | 129篇 |
1976年 | 116篇 |
1975年 | 108篇 |
1974年 | 135篇 |
1973年 | 135篇 |
1972年 | 111篇 |
1971年 | 119篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
51.
Agonist-stimulated oscillations and cycling of intracellular free calcium in individual cultured muscle cells 总被引:7,自引:0,他引:7
Receptor regulation of [Ca2+]i was monitored in individual BC3H-1 muscle cells with intracellularly trapped fura-2 using digital imaging analysis techniques. Activation of alpha 1-adrenergic or H1-histaminergic receptors resulted in multiple bursts, or oscillations, of elevated [Ca2+]i with an average interval frequency of approximately 1.8 min-1. The duration of oscillatory behavior was generally more prolonged in response to phenylephrine than in response to histamine. Additionally, a larger fraction of the cells responded with [Ca2+]i oscillations to phenylephrine (approximately 90%) than to histamine (approximately 60%), although the majority of cells produced oscillations in response to both agonists. In most cells, the receptor-mediated [Ca2+]i oscillations continued for several minutes in the absence of extracellular Ca2+, although the amplitude of the individual peaks gradually decreased. The activation of [Ca2+]i oscillations by H1-receptors was more dependent upon extracellular Ca2+ than those elicited by alpha 1-receptors, reflecting the greater dependency of the histaminergic response on Ca2+ influx. Readdition of Ca2+ to the incubation buffer resulted in the resumption of the [Ca2+]i oscillations. These results indicate that considerable cycling of Ca2+ between the cytoplasm and the endoplasmic reticulum must occur. Receptor-mediated [Ca2+]i oscillations were much more prevalent in subconfluent cells than in confluent cells, possibly due to increased coupling of the cells at higher densities. The cells were capable of responding independently of one another, since sister cells displayed unique temporal responses immediately following cell division. Thus, the linkage of receptor occupancy to [Ca2+]i elevation is a functionally unique property for each individual cell and can be influenced by epigenetic factors. 相似文献
52.
From the measures of evolutionary distance between pairs ofsequences in a set, it is possible to infer the genetic treeor trees which best fit these known data. DENDRON is a new program,written in FORTRAN 66, which computes an initial tree from thebottom-up, then searches among increasingly divergent treesfor a better fit. As a check on the consistency of the measures,the program tests all triplets for the triangle inequality.DENDRON also calculates a single top-down tree,progressing from the trunk to the twigs, for comparison withthe bottom-up trees.
Received on August 17, 1987; accepted on June 1, 1988 相似文献
53.
E R Taylor 《Journal of biomolecular structure & dynamics》1992,10(3):533-550
An alternate model for surface noncovalent and surface covalent binding of aflatoxin B1 to N(7) of guanine in DNA is proposed. This model considers the out-of-plane motions of C(8) of aflatoxin B1 in those interactions. The covalent intercalated fit of aflatoxin B1 into DNA arises from steric adjustments made by DNA at the covalent intercalation site as well as local strain in the bond angles about N(7) of guanine and C(8) of aflatoxin B1. The bond angle about N(7) deviates modestly from the sp2 value toward the sp3 value. This study suggests that the surface covalent aflatoxin B1-DNA complex serves only a minor role in aflatoxin's precarcinogenic interaction with DNA and is a likely correctable error. 相似文献
54.
Observation of a polar bear with rabies 总被引:1,自引:0,他引:1
On 1 November 1989 the first confirmed case of rabies in a polar bear (Ursus maritimus) was encountered by Inuit hunters in the vicinity of Cape Kendall, Southampton Island, Northwest Territories (Canada). The adult male polar bear had posterior paralysis. Rabies was detected by mouse inoculation and a positive immunoperoxidase reaction on spinal cord and Gasserian ganglion from the bear. Histologic lesions in the lumbar region of the spinal cord were consistent with the posterior paralysis. The impact of rabies on the population dynamics of polar bears probably is minimal. Rabies in polar bears constitutes a potential health hazard for polar bear hunters. 相似文献
55.
S. Taylor 《BMJ (Clinical research ed.)》1992,305(6868):1585-1586
56.
Regulatory mechanisms in bradykinin (BK) activated release of arachidonate (ARA) and synthesis of prostaglandin (PG) and platelet activating factor (PAF) were studied in bovine pulmonary artery endothelial cells (BPAEC). A role for GTP binding protein (G-protein) in the binding of BK to the cells was determined. Guanosine 5-O- (thiotriphosphate), (GTPtauS), lowered the binding affinity for BK and increased the Kd for the binding from 0.45 to 1.99 nM. The Bmax remained unaltered at 2.25 x 10(-11) mole. Exposure of the cells to aluminium fluoride also reduced the affinity for BK. Bradykinin-induced release of ARA proved pertussis toxin (PTX) sensitive, with a maximum sensitivity at 10 ug/ml PTX. GTPtauS at 100 muM increased the release of arachidonate. The effect of GTPtauS and BK was additive at suboptimal doses of BK up to 0.5 nM but never exceeded the levels of maximal BK stimulation at 50 nM. PTX also inhibited the release of ARA induced by the calcium ionophore, A23187. Phorbol 12-myristate 13-acetate or more commonly known as tetradecanoyl phorbol acetate (TPA) itself had little effect on release by the intact cells. However, at 100 nM it augmented the BK activated release. This was downregulated by overnight exposure to TPA and correlated with down-regulation of protein kinase C (PKC) activity. The down-regulation only affected the augmentation of ARA release by TPA but not the original BK activated release. TPA displayed a similar, but more potent amplification of PAF synthesis in response to both BK or the calcium ionophore A23187. These results taken together point to the participation of G-protein in the binding of BK to BPAEC and its activation of ARA release. Possibly two types of G-protein are involved, one associated with the receptor, the other activated by Ca(2+) and perhaps associated with phospholipase A(2) (PLA(2)). Our results further suggest that a separate route of activation, probably also PLA(2) related, takes place through a PKC catalysed phosphorylation. 相似文献
57.
J. H. Exton S. J. Taylor G. Augert S. B. Bocckino 《Molecular and cellular biochemistry》1991,104(1-2):81-86
There is much evidence that G-proteins transduce the signal from receptors for Ca2+-mobilizing agonists to the phospholipase C that catalyzes the hydrolysis of phosphoinositides. However, the specific G-proteins involved have not been identified. We have recently purified a 42 kDa protein from liver that activates phosphoinositide phospholipase C and cross-reacts with antisera to a peptide common to G-protein -subunits. It is proposed that this protein is the a-subunit of the G-protein that regulates the phospholipase in this tissue.Ca2+-mobilizing agonists and certain growth factors also promote the hydrolysis of phosphatidylcholine through the activation of phospholipases C and D in many cell types. This yields a larger amount of diacylglycerol for a longer time than does the hydrolysis of inositol phospholipids. Consequently phosphatidylcholine breakdown is probably a major factor in long-term regulation of protein kinase C. The functions of phosphatidic acid produced by phospholipase D are speculative, but there is evidence that it is a major source of diacylglycerol in many cell types. The regulation of phosphatidylcholine phospholipases is multiple and involves direct activation by G-proteins, and regulation by Ca2+ protein kinase C and perhaps growth factor receptor tyrosine kinases. 相似文献
58.
A family of muscle gene promoter element (CArG) binding activities in Xenopus embryos: CArG/SRE discrimination and distribution during myogenesis. 总被引:4,自引:0,他引:4 下载免费PDF全文
M V Taylor 《Nucleic acids research》1991,19(10):2669-2675
The CArG box is an essential promoter sequence for cardiac muscle actin gene expression in Xenopus embryos. To assess the role of the CArG motif in promoter function during Xenopus development, the DNA-binding activities present in the embryo that interact with this sequence have been investigated. A family of four Embryo CArG box1 Factors (ECFs) was separated by a 2-step fractionation procedure. These factors were distinct from the previously described C-ArG box binding activity Serum Response Factor (SRF). ECF1 was the most prominent binding activity in cardiac actin-expressing tissues, and bound the CArG box in preference to a Serum Response Element (SRE). SRF was also detectable in muscle, but it bound preferentially to an SRE. The properties of ECF3 were similar to those of ECF1, but it was much less prominent in cardiac actin-expressing tissues. The properties of the two other factors were distinctive: ECF2 was of relatively low affinity and high abundance, whilst ECF4 bound non-specifically to ends of DNA. The binding activity (or activities) that interacted with the CArG box was found to be influenced by both the concentrations of the other CArG box binding activities and the sequence of the site. Although there was no evidence for a muscle-specific CArG box binding activity, the properties of ECF1 suggest that it could play a role in the expression of the cardiac actin gene during Xenopus development. 相似文献
59.
In vitro and in vivo inhibition of human small cell lung carcinoma (NCI-H69) growth by a somatostatin analogue 总被引:1,自引:0,他引:1
J E Taylor A E Bogden J P Moreau D H Coy 《Biochemical and biophysical research communications》1988,153(1):81-86
An endocrinologically-potent octapeptide analogue of somatostatin (SRIF), 3-(2-naphthyl)-D-Ala-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (BIM-23014 C), was examined for its ability to inhibit the in vitro and in vivo growth of the human small cell lung carcinoma (SCLC) line, NCI-H69. When cultured cells were implanted into athymic nude mice, treatment (500 micrograms/injection, twice daily) resulted in a prolongation of lag time for the appearance of measurable tumors, and there was a marked inhibition of the growth rate. Indeed, peptide injection in the region of the tumor resulted in a complete regression of the NCI-H69 tumors. Withdrawal of BIM-23014 C treatment resulted in an acceleration of tumor growth indicating an antiproliferative rather the oncolytic action. A similar inhibition of tumor growth was also observed when solid tumors obtained from the first implantation were used as the donor tissues. In cell culture, the proliferation in the presence of a low concentration (10nM) of BIM-23104 C was also significantly retarded suggesting a direct mechanism of action. 相似文献
60.
Chromosomal localization of Emv-16 and Emv-17, two closely linked ecotropic proviruses of RF/J mice. 总被引:4,自引:1,他引:3 下载免费PDF全文
Emv-16 and Emv-17, the two closely linked ecotropic proviral loci of RF/J mice, have been mapped to chromosome 1 between leaden, ln, and the mouse engrailed homeo-box locus, En-1, by using recombinant inbred strains and conventional backcross analysis. 相似文献