全文获取类型
收费全文 | 5492篇 |
免费 | 698篇 |
国内免费 | 2篇 |
专业分类
6192篇 |
出版年
2022年 | 86篇 |
2021年 | 111篇 |
2020年 | 71篇 |
2019年 | 85篇 |
2018年 | 87篇 |
2017年 | 77篇 |
2016年 | 139篇 |
2015年 | 200篇 |
2014年 | 223篇 |
2013年 | 258篇 |
2012年 | 327篇 |
2011年 | 356篇 |
2010年 | 173篇 |
2009年 | 177篇 |
2008年 | 262篇 |
2007年 | 259篇 |
2006年 | 217篇 |
2005年 | 215篇 |
2004年 | 180篇 |
2003年 | 163篇 |
2002年 | 175篇 |
2001年 | 138篇 |
2000年 | 128篇 |
1999年 | 139篇 |
1998年 | 54篇 |
1997年 | 60篇 |
1996年 | 55篇 |
1995年 | 44篇 |
1994年 | 60篇 |
1993年 | 37篇 |
1992年 | 91篇 |
1991年 | 67篇 |
1990年 | 73篇 |
1989年 | 80篇 |
1988年 | 88篇 |
1987年 | 86篇 |
1986年 | 74篇 |
1985年 | 80篇 |
1984年 | 56篇 |
1983年 | 58篇 |
1982年 | 58篇 |
1981年 | 46篇 |
1980年 | 38篇 |
1979年 | 58篇 |
1978年 | 42篇 |
1977年 | 46篇 |
1975年 | 45篇 |
1974年 | 44篇 |
1973年 | 55篇 |
1972年 | 43篇 |
排序方式: 共有6192条查询结果,搜索用时 0 毫秒
1.
Epithelial ovarian carcinoma (EOC), the major cause of gynaecological cancer death, is a heterogeneous disease classified into five subtypes. Each subtype has distinct clinical characteristics and is associated with different genetic risk factors and molecular events, but all are treated with surgery and platinum/taxane regimes. Tumour progression and chemoresistance is generally associated with major metabolic alterations, notably altered mitochondrial function(s). Here, we report for the first time that the expression of the mitochondrial regulators PGC1α and TFAM varies between EOC subtypes; furthermore, we have identified a profile in clear-cell carcinoma consisting of undetectability of PGC1α/TFAM, and low ERα/Ki-67. By contrast, high-grade serous carcinomas were characterised by a converse state of PGC1α/TFAM, ERα positivity and a high Ki-67 index. Interestingly, loss of PGC1α/TFAM and ERα was found also in a non-clear cell EOC cell line made highly resistant to platinum in vitro. Similar to clear-cell carcinomas, these resistant cells also showed accumulation of glycogen. Altogether, our data provide mechanistic insights into the chemoresistant nature of ovarian clear-cell carcinomas. Furthermore, these findings corroborate the need to take into account the diversity of EOC and to develop subtype specific treatment strategies. 相似文献
2.
3.
Endonuclease II of bacteriophage T4 is required for in vivo restriction of cytosine-containing DNA from its host, Escherichia coli, (as well as from phage mutants lacking cytosine modification), normally the first step in the reutilization of host DNA nucleotides for synthesis of phage DNA in infected cells. The phage cytosine-DNA is fragmented incompletely to yield genetically defined fragments. This restriction is different from that of type I, II, or III restriction enzymes. We have located seven major endonuclease II-dependent restriction sites in the T4 genome, of which three were analyzed in detail; in addition, abundant sites were cleaved in less than or equal to 5% of all molecules. Sites I, II, and III shared the sequence 5'-CCGNNTTGGC-3' and were cleaved in about 25% (I and III) and 65% (II) of all molecules, predominantly staggered around the first or second of the central unspecified base pairs to yield fragments with one 5' base. The less frequently cleaved sites I and III deviated from site II in predicted helical structure when viewed from the consensus strand, and in sequence when viewed from the opposite strand. Thus, interaction with a particular helical structure as well as recognition of the bases in DNA appears important for efficient cleavage. 相似文献
4.
5.
6.
J A Katzenellenbogen K E Carlson B S Katzenellenbogen 《Journal of steroid biochemistry》1985,22(5):589-596
In many estrogen responsive systems the isomers of tamoxifen are known to have different biological character-the trans isomer is generally an antagonist and the cis isomer an agonist. Attempts to similarly characterize the isomers of hydroxytamoxifen (which differ greatly in their affinity for the estrogen receptor) are shown to be complicated by their facile isomerization. This isomerization was studied in cultures of estrogen receptor positive MCF-7 human breast cancer cells and monitored by HPLC under reversed phase conditions. Hydroxytamoxifen isomers that are initially 99% pure, undergo a time and temperature dependent isomerization, so that after 2 days in tissue culture medium at 37 degrees C they have isomerized to the extent of 20%. This isomerization occurs in the cell-free medium alone and cannot be attributed to a metabolic conversion by the cells. The isomerization occurs much more slowly at 4 than at 37 degrees C and can be reduced considerably by various antioxidants (butylated hydroxytoluene, ascorbate, alpha-tocopherol, retinoic acid and retinal); however, at concentrations that block isomerization, these antioxidants are toxic to the cells. Although the medium contains both the cis and trans isomers of hydroxytamoxifen, the MCF-7 cells preferentially accumulate the trans isomer and the material associated with the nuclear estrogen receptor is, in all cases, mainly the higher affinity trans isomer. A similar preference of the estrogen receptor for the trans isomer is seen with diethylstilbestrol, resulting again in almost exclusive accumulation of the trans isomer in the receptor binding site. These experiments indicate the importance of verifying the isomer compositions of easily isomerizable non-steroidal estrogens and antiestrogens, such as diethylstilbestrol and hydroxytamoxifen, both in stock solutions and in experimental samples (especially those derived from receptor-associated material), so as to ascertain that the activity of the individual isomers is being correctly assigned. 相似文献
7.
8.
A Banerjee M A Jordan R F Luduena 《Biochemical and biophysical research communications》1985,128(2):506-512
Incubation of phosphocellulose-purified tubulin with GSH at 30 degrees C results in an inhibition of colchicine binding activity. GSSG has a protective effect against the GSH-induced loss of colchicine-binding. Incubation of tubulin with GSH at 30 degrees C results in the formation of abnormal tubulin polymers which are insensitive to cold. Such aggregation is insensitive to antimicrotubular drugs. Aggregation is inhibited by GSSG but not by DTT or mercaptoethanol. GSH-induced aggregation is very sensitive to the ionic strength of the assembly medium; both the aggregation and colchicine binding inhibition induced by GSH are inhibited at higher ionic strength. These results indicate a very complex interaction of GSH with tubulin. 相似文献
9.
10.
Growth rate differences between resident native brook trout and non-native brown trout 总被引:1,自引:0,他引:1
Between species and across season variation in growth was examined by tagging and recapturing individual brook trout Salvelinus fontinalis and brown trout Salmo trutta across seasons in a small stream (West Brook, Massachusetts, U.S.A.). Detailed information on body size and growth are presented to (1) test whether the two species differed in growth within seasons and (2) characterize the seasonal growth patterns for two age classes of each species. Growth differed between species in nearly half of the season- and age-specific comparisons. When growth differed, non-native brown trout grew faster than native brook trout in all but one comparison. Moreover, species differences were most pronounced when overall growth was high during the spring and early summer. These growth differences resulted in size asymmetries that were sustained over the duration of the study. A literature survey also indicated that non-native salmonids typically grow faster than native salmonids when the two occur in sympatry. Taken together, these results suggest that differences in growth are not uncommon for coexisting native and non-native salmonids. 相似文献