全文获取类型
收费全文 | 14771篇 |
免费 | 1282篇 |
国内免费 | 11篇 |
专业分类
16064篇 |
出版年
2023年 | 72篇 |
2022年 | 147篇 |
2021年 | 290篇 |
2020年 | 152篇 |
2019年 | 209篇 |
2018年 | 283篇 |
2017年 | 220篇 |
2016年 | 388篇 |
2015年 | 635篇 |
2014年 | 727篇 |
2013年 | 959篇 |
2012年 | 1084篇 |
2011年 | 1119篇 |
2010年 | 694篇 |
2009年 | 621篇 |
2008年 | 898篇 |
2007年 | 913篇 |
2006年 | 844篇 |
2005年 | 785篇 |
2004年 | 780篇 |
2003年 | 745篇 |
2002年 | 656篇 |
2001年 | 209篇 |
2000年 | 169篇 |
1999年 | 216篇 |
1998年 | 205篇 |
1997年 | 131篇 |
1996年 | 109篇 |
1995年 | 119篇 |
1994年 | 127篇 |
1993年 | 116篇 |
1992年 | 128篇 |
1991年 | 111篇 |
1990年 | 113篇 |
1989年 | 110篇 |
1988年 | 95篇 |
1987年 | 70篇 |
1986年 | 69篇 |
1985年 | 66篇 |
1984年 | 69篇 |
1983年 | 64篇 |
1982年 | 58篇 |
1981年 | 57篇 |
1980年 | 58篇 |
1979年 | 50篇 |
1978年 | 39篇 |
1977年 | 41篇 |
1976年 | 29篇 |
1974年 | 32篇 |
1973年 | 29篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
In an experimental strain of white plumage geese created in 1989, two experiments were carried out from 1993 to 1995 in order to estimate genetic parameters for growth, and carcass composition traits in non-overfed animals, and genetic parameters for growth and fatty liver formation in overfed animals. Four hundred and thirty-one non-overfed animals were bred and slaughtered at 11 weeks of age; they were measured for forearm length, keel bone length, chest circumference and breast depth before and after slaughtering. The carcasses were partly dissected in order weigh breast, breast muscle and skin + fat, and abdominal fat. Four hundred and seventy-seven overfed animals were slaughtered at 20 weeks of age; they were measured for "paletot" (breast meat, bone and meat from wings, bone and meat from thigh and legs) weight and liver weight. In these two experiments, the weights had moderate to high heritability values. Breast depth measured on live animals showed a low heritability value. In overfed animals, liver weight showed a high heritability value. Liver weight could be increased by selection without a great effect on "paletot" weight. Thus, obtaining a white plumage geese strain for fatty liver production by selection would be difficult because only 20% of overfed animals had fatty liver. The results did not allow to conclude on the influence of selection on liver weight on carcass traits such as muscle or fatty tissue weight. 相似文献
992.
993.
The SPO11/TOPVIA family includes proteins from archaebacteria and eukaryotes. The protein member from the archaebacterium Sulfulobus shibatae is the catalytic subunit of TopoVI DNA topoisomerase. In Saccharomyces cerevisiae, Schizosaccharomyces pombe, Caenorhabditis elegans and Drosophila melanogaster, SPO11 is required for meiotic recombination, suggesting a conserved mechanism for the initiation step of this process. Indeed, S. cerevisiae SPO11 has been shown to be directly involved in the formation of meiotic DNA double-strand breaks that initiate meiotic recombination.
Here, we report the identification of a Mus musculus Spo11 cDNA, which encodes a protein closely related to all members of the SPO11/TOPVIA family. cDNAs resulting from alternative
splicing were detected, suggesting that there are potential variants of the mouse SPO11 protein. By RNA-blotting analysis,
expression of the mouse Spo11 gene was detected only in the testis, in agreement with its predicted function in the initiation of meiotic recombination.
We mapped the mouse Spo11 gene to chromosome 2, band H2–H4.
Received: 11 August 1999; in revised form; 11 October 1999 / Accepted: 13 October 1999 相似文献
994.
New advances in coenzyme Q biosynthesis 总被引:2,自引:0,他引:2
Catherine F. Clarke 《Protoplasma》2000,213(3-4):134-147
Summary Coenzyme Q (or ubiquinone) is the product of two distinct biosynthetic pathways: the lipid tail of coenzyme Q is formed via the isoprene biosynthetic pathway, and the quinone ring derives from the metabolism of either shikimic acid or tyrosine. In general, eukaryotic organisms use the classical mevalonate pathway to form isopentenyl- and dimethylallyl-diphosphate, the five carbon building blocks of the polyisoprenoid tail, and prokaryotes use 1-deoxy-D-xylulose-5-phosphate, formed via the Rohmer pathway. The quinone ring precursor is 4-hydroxybenzoic acid, which is formed directly from chorismate inSaccharomyces cerevisiae andEscherichia coli, or from tyrosine in animal cells. Ring modification steps including prenylation, decarboxylation, and successive hydroxylation and methylation steps form the fully substituted benzoquinone ring of coenzyme Q. Many of the genes and polypeptides involved in coenzyme Q biosynthesis have been isolated and characterized by utilizing strains ofE. coli andS. cerevisiae with mutations in theubi andCOQ genes, respectively. This article reviews recent progress in characterizing the biosynthesis of coenzyme Q inE. coli, S. cerevisiae, and other eukaryotic organisms. 相似文献
995.
Gonzalez LC Pinilla L Tena-Sempere M Dieguez C Casanueva FF Aguilar E 《Journal of reproduction and fertility》2000,118(1):39-45
Recent data indicate that leptin is involved in the control of reproductive function. Experiments were carried out to analyse the role of endogenous leptin in the regulation of LH and prolactin secretion during the afternoon of pro-oestrus and that induced by ovarian steroids in ovariectomized rats. In the first experiment, cyclic female rats were implanted with intra-auricular and intracerebroventricular (i.c.v.) cannulae and, at pro-oestrus, were injected (i.c.v.) with 10 microliters normal rabbit serum or leptin antiserum (at 13:00 and 14:00 h). Blood samples were obtained at 10:00 h and at intervals of 1 h between 13:00 and 20:00 h. In the second experiment, female rats in pro-oestrus were injected with normal rabbit serum or leptin antiserum at 16:00 and 18:00 h and blood samples were taken every 10 min between 18:00 and 20:00 h. In the third experiment, adult female rats that had been ovariectomized 2 weeks before were implanted with intra-auricular and i.c.v. cannulae and treated with oestradiol benzoate (30 micrograms s.c.) at 10:00 h and progesterone (2 mg s.c.) 48 h later. Normal rabbit serum (10 microliters) or leptin antiserum (10 microliters) were injected (i.c.v.) at 13:00 and 14:00 h, and blood samples were obtained at 10:00 h and at intervals of 1 h between 13:00 and 20:00 h. In the fourth experiment, hemipituitaries from ovariectomized steroid-treated female rats were incubated in the presence of leptin116-130 (an active fragment of the native molecule), GnRH or leptin + GnRH. Prolactin and LH secretion during the afternoon of pro-oestrus in females treated with leptin antiserum was similar to that observed in animals injected with normal rabbit serum. In ovariectomized female rats, the steroid-induced LH surge increased slightly after administration of leptin antiserum, whereas the prolactin surge remained unchanged. In vitro, leptin116-130 (10(-5) to 10(-8) mol l-1) inhibited LH secretion and modulated the effect of GnRH on LH release, depending on the concentration of GnRH: leptin116-130 (10(-6) mol l-1) reduced the effectiveness of 10(-7) mol GnRH l-1 and increased that of 10(-9) mol GnRH l-1. In conclusion, these experiments indicate that acute immunoneutralization of endogenous leptin does not interfere with spontaneous or steroid-induced LH and prolactin surges. In addition, the finding that leptin116-130 inhibited LH release and modulated the effectiveness of GnRH in vitro provides evidence of the direct modulatory role of leptin on LH secretion acting at the pituitary. 相似文献
996.
Cocaine N-demethylation to norcocaine was studied in human liver microsomes of different ages. Norcocaine was formed at a considerable rate in fetal (45.4+/-18.2 nmol/mg x hour, n = 8) and adult specimens (82.0+/-46.6 nmol/mg x hour, n = 15), p = 0.04 (Mann-Whitney). Furthermore, the apparent Km values in fetal specimens (0.57 and 0.48 mM, n = 2) showed a higher affinity compared with those of adults (mean value 2.7 (1.8-4.25) mM, n = 4). Estimated enzyme metabolic clearance with respect to P450 total content was higher in fetal than in adult liver microsomes (2.22 ml/nmol P450 x hour, and 0.18 (0.14-0.23) ml/nmol P450 x hour, respectively). Several drugs, known to be CYP3A substrates, were used as potential inhibitors of cocaine metabolism. Midazolam, ergotamine and erythromycin showed strong inhibition (approx. 70 %) when used at concentrations of 500 microM (midazolam, erythromycin) or 200 microM (ergotamine). The metabolism of 1 mM cocaine correlated strongly with immunodetected CYP3A protein determined by Western blotting in both fetal (r = 0.89, p = 0.19) and adult specimens (r = 0.82, p < 0.01) . These findings further support CYP3A as a major catalyst of norcocaine formation in human liver microsomes. These results are important given the potential risk of toxicity to the foetus of maternal cocaine abuse during pregnancy. Although the high Km values found in adult livers reduce the importance of this enzyme pathway in cocaine detoxication, this pathway would emerge as significant in circumstances of CYP3A induction and/or drug interactions leading to potential liver toxicity in chronic cocaine abusers. 相似文献
997.
The microtubular element of the plant cytoskeleton undergoes dramatic architectural changes in the course of the cell cycle, specifically at the entry into and exit from mitosis. These changes underlie the acquisition of specialized properties and functions involved, for example, in the equal segregation of chromosomes and the correct positioning and formation of the new cell wall. Here we review some of the molecular mechanisms by which the dynamics and the organization of microtubules are regulated and suggest how these mechanisms may be under the control of cell cycle events. 相似文献
998.
Sterol Uptake in Saccharomyces cerevisiae Heme Auxotrophic Mutants Is Affected by Ergosterol and Oleate but Not by Palmitoleate or by Sterol Esterification 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《Journal of bacteriology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Frdrique Ness Tilman Achstetter Catherine Duport Francis Karst Roberto Spagnoli Eric Degryse 《Journal of bacteriology》1998,180(7):1913-1919
The relationship between sterol uptake and heme competence in two yeast strains impaired in heme synthesis, namely, G204 and H12-6A, was analyzed. To evaluate heme availability, a heterologous 17α-hydroxylase cytochrome P-450 cDNA (P-450c17) was expressed in these strains, and its activity was measured in vivo. Heme deficiency in G204 led to accumulation of squalene and lethality. The heterologous cytochrome P-450 was inactive in this strain. The leaky H12-6A strain presented a slightly modified sterol content compared to that for the wild type, and the P-450c17 recovered partial activity. By analyzing sterol transfer on nongrowing cells, it was shown that the cells were permeable toward exogenous cholesterol when they were depleted of endogenous sterols, which was the case for G204 but not for H12-6A. It was concluded that the fully blocked heme mutant (G204) replenishes its diminishing endogenous sterol levels during growth by replacement with sterol from the outside medium. Endogenous sterol biosynthesis appears to be the primary factor capable of excluding exogenous sterol. Oleate but not palmitoleate was identified as a component that reduced but did not prevent sterol transfer. Sterol transfer was only slightly affected by a lack of esterification. It is described herein how avoidance of the potential cytotoxicity of the early intermediates of the mevalonate pathway could be achieved by a secondary heme mutation in erg auxotrophs. 相似文献
999.
We describe genetic interactions between mutations in mgr, asp, and polo, genes required for the correct behaviour of the spindle poles in Drosophila. The phenotype of a polo
1
mgr double mutant is more similar to mgr than polo
1
, but the frequency of circular monopolar figures (CMFs) seen with either mutant alone is additive, suggesting that the two
gene products are required for independent functions in the formation of bipolar spindles. The asp
E3
mgr double mutant arrests much earlier in development than either mutant alone, indicative of a strong block to cell proliferation.
We discuss whether the lack of microtubular structures in these cells reflects an extended mitotic arrest, or if it is a more
direct consequence of the double mutant combination. A polo
1
asp
E3
double mutant shows a dramatic synergistic increase in mitotic frequency. The loss of CMFs normally associated with the polo
1
phenotype suggests that the Asp microtubule-associated protein is required to maintain the structure of spindle poles. We
speculate that Asp protein might be a substrate for the serine-threonine protein kinase encoded by polo.
Received: 8 August 1998 / Accepted: 13 September 1998 相似文献
1000.
OCI-5/GPC3, a Glypican Encoded by a Gene That Is Mutated in the Simpson-Golabi-Behmel Overgrowth Syndrome, Induces Apoptosis in a Cell Line–specific Manner
下载免费PDF全文
![点击此处可从《The Journal of cell biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Alfonso Dueas Gonzalez Mitsunori Kaya Wen Shi Howard Song Joseph R. Testa Linda Z. Penn Jorge Filmus 《The Journal of cell biology》1998,141(6):1407-1414
OCI-5/GPC3 is a member of the glypican family. Glypicans are heparan sulfate proteoglycans that are bound to the cell surface through a glycosyl-phosphatidylinositol anchor. It has recently been shown that the OCI-5/GPC3 gene is mutated in patients with the Simpson-Golabi-Behmel Syndrome (SGBS), an X-linked disorder characterized by pre- and postnatal overgrowth and various visceral and skeletal dysmorphisms. Some of these dysmorphisms could be the result of deficient growth inhibition or apoptosis in certain cell types during development. Here we present evidence indicating that OCI-5/GPC3 induces apoptosis in cell lines derived from mesothelioma (II14) and breast cancer (MCF-7). This induction, however, is cell line specific since it is not observed in NIH 3T3 fibroblasts or HT-29 colorectal tumor cells. We also show that the apoptosis-inducing activity in II14 and MCF-7 cells requires the anchoring of OCI-5/GPC3 to the cell membrane. The glycosaminoglycan chains, on the other hand, are not required. MCF-7 cells can be rescued from OCI-5/GPC3–induced cell death by insulin-like growth factor 2. This factor has been implicated in Beckwith-Wiedemann, an overgrowth syndrome that has many similarities with SGBS. The discovery that OCI-5/GPC3 is able to induce apoptosis in a cell line– specific manner provides an insight into the mechanism that, at least in part, is responsible for the phenotype of SGBS patients. 相似文献