全文获取类型
收费全文 | 3035篇 |
免费 | 331篇 |
国内免费 | 3篇 |
出版年
2021年 | 24篇 |
2020年 | 26篇 |
2019年 | 27篇 |
2018年 | 30篇 |
2017年 | 34篇 |
2016年 | 47篇 |
2015年 | 97篇 |
2014年 | 81篇 |
2013年 | 106篇 |
2012年 | 130篇 |
2011年 | 111篇 |
2010年 | 94篇 |
2009年 | 61篇 |
2008年 | 117篇 |
2007年 | 126篇 |
2006年 | 110篇 |
2005年 | 107篇 |
2004年 | 92篇 |
2003年 | 99篇 |
2002年 | 127篇 |
2001年 | 106篇 |
2000年 | 123篇 |
1999年 | 110篇 |
1998年 | 67篇 |
1997年 | 36篇 |
1996年 | 49篇 |
1995年 | 32篇 |
1994年 | 31篇 |
1993年 | 46篇 |
1992年 | 76篇 |
1991年 | 78篇 |
1990年 | 76篇 |
1989年 | 57篇 |
1988年 | 61篇 |
1987年 | 58篇 |
1986年 | 54篇 |
1985年 | 39篇 |
1984年 | 52篇 |
1983年 | 40篇 |
1982年 | 41篇 |
1981年 | 35篇 |
1979年 | 38篇 |
1978年 | 37篇 |
1976年 | 32篇 |
1975年 | 48篇 |
1974年 | 29篇 |
1973年 | 26篇 |
1972年 | 36篇 |
1971年 | 25篇 |
1967年 | 23篇 |
排序方式: 共有3369条查询结果,搜索用时 15 毫秒
71.
The DNA sequence of the wild type S. typhimurium parE gene was determined. The predicted protein has 96.7% amino acid identity with the ParE protein of E.coli, but is 29 amino acids longer, due to an additional basepair in the 3' end of the S. typhimurium gene. Subclones of the S. typhimurium parE gene localized the sites of four heat sensitive mutations within parE. The parE206 and parE374 mutations are identical (Val67-Met) and lie in a highly conserved region corresponding to the ATP binding pocket of GyrB. Two additional heat sensitive mutations were sequenced and predict the following amino acid substitutions: parE377 (Gly399-Ser) and parE493 (Thr583-Pro). All of the heat sensitive mutations lie in regions with strong amino acid homology to GyrB. 相似文献
72.
Recruitment of epidermal growth factor and transferrin receptors into coated pits in vitro: differing biochemical requirements. 总被引:10,自引:1,他引:9
下载免费PDF全文
![点击此处可从《Molecular biology of the cell》网站下载免费的PDF全文](/ch/ext_images/free.gif)
The biochemical requirements for epidermal growth factor (EGF) and transferrin receptor-mediated endocytosis were compared using perforated human A431 cells. Morphological studies showed that horseradish peroxidase (HRP)-conjugated EGF and gold-labeled antitransferrin (Tfn) receptor antibodies were colocalized during endocytosis in vitro. The sequestration of both ligands into deeply invaginated coated pits required ATP hydrolysis and cytosolic factors and was inhibited by GTP gamma S, indicating mechanistic similarities. Importantly, several differences in the biochemical requirements for sequestration of EGF and Tfn were also detected. These included differing requirements for soluble AP (clathrin assembly protein) complexes, differing cytosolic requirements, and differing sensitivities to the tyrosine kinase inhibitor, genistein. The biochemical differences detected between EGF and Tfn sequestration most likely reflect specific requirements for the recruitment of EGF-receptors (R) into coated pits. This assay provides a novel means to identify the molecular bases for these biochemical distinctions and to elucidate the mechanisms involved in ligand-induced recruitment of EGF-R into coated pits. 相似文献
73.
Jörg Schmid Peter Möller Gerd Moldenhauer Bernd Dörken Heiner Bihl Siegfried Matzku 《Cancer immunology, immunotherapy : CII》1993,36(4):274-280
Accumulation of radiolabelled monoclonal antibodies (mAb) in human B-lymphoma xenografts was found to result in two distinct patterns. The basic elements leading to these patterns were elucidated by autoradiographic and immunohistological analysis applied to the nude mouse xenografts BJAB and OCI.LY1. With BJAB, accumulation occurred exclusively in peripheral cell layers of the lymphoma nodule, while central areas were not accessible irrespective of mAb dose. This feature was the consequence of an inefficient transport across intratumoral vessels together with peripheral mAb supply through a subcapsular pseudosinus. With OCI.LY1, intratumoral vessels showed generalized leakiness. Furthermore, interstitial transport was operative to a fair extent, such that in early images multiple sites of mAb extravasation were obvious, which coalesced during the course of prolonged uptake. The pattern of peripheral mAb uptake resulted in a low overall tumour uptake, while multifocal uptake yielded substantial accumulation values. 相似文献
74.
75.
Schmid SL 《Trends in cell biology》1993,3(5):145-148
Cell-free systems provide essential tools for elucidating the molecular mechanisms underlying complex cellular processes such as vesicular transport. The biochemical utility of these model systems is strengthened by assays that allow rapid, quantitative detection of the events being studied. Two model systems have recently been developed to reconstitute coated-vesicle budding, and two different biochemical assays are used to detect this event. Striking differences in the biochemical requirements for 'coated-vesicle budding' are detected by these two assays, suggesting that two distinct events are being measured. These findings have wide implications for the use of cell-free assay systems in cell biology. 相似文献
76.
Lorenz Schmid Michel Bottlaender Chantal Fuseau Denis Fournier Emmanuel Brouillet Mariannick Mazire 《Journal of neurochemistry》1995,65(4):1880-1886
Abstract: The distinctive pharmacological activity of zolpidem in rats compared with classical benzodiazepines has been related to its differential affinity for benzodiazepine receptor (BZR) subtypes. By contrast, in nonhuman primates the pharmacological activity of zolpidem was found to be quite similar to that of classical BZR agonists. In an attempt to explain this discrepancy, we examined the ability of zolpidem to differentiate BZR subtypes in vivo in primate brain using positron emission tomography. The BZRs were specifically labeled with [11C]flumazenil. Radiotracer displacement by zolpidem was monophasic in cerebellum and neocortex, with in vivo Hill coefficients close to 1. Conversely, displacement of [11C]flumazenil was biphasic in hippocampus, amygdala, septum, insula, striatum, and pons, with Hill coefficients significantly smaller than 1, suggesting two different binding sites for zolpidem. In these cerebral regions, the half-maximal inhibitory doses for the high-affinity binding site were similar to those found in cerebellum and neocortex and ~100-fold higher for the low-affinity binding site. The low-affinity binding site accounted for <32% of the specific [11C]-flumazenil binding. Such zolpidem binding characteristics contrast with those reported for rodents, where three different binding sites were found. Species differences in binding characteristics may explain why zolpidem has a distinctive pharmacological activity in rodents, whereas its pharmacological activity in primates is quite similar to that of classical BZR agonists, except for the absence of severe effects on memory functions, which may be due to the lack of substantial zolpidem affinity for a distinct BZR subtype in cerebral structures belonging to the limbic system. 相似文献
77.
Kurt W. Schmid Birgit Kunk Rudolf Kirchmair Martin T?tsch Werner B?cker Reiner Fischer-Colbrie 《The Histochemical journal》1995,27(6):473-481
Summary An antiserum raised against a synthetic peptide derived from the primary amino sequence of rat secretogranin II (chromogranin
C) was used for immunological (quantitative radioimmunoassay analysis) and immunohistochemical studies of normal human endocrine
and nervous tissues. This antibody recognized a novel and biologically active neuropeptide which was coined as secretoneurin.
In endocrine tissues, secretoneurin was mainly co-localized with chromogranin A and B with some exceptions (e.g., parathyroid
gland). Secretoneurin was demonstrated immunohistochemically in the adrenal medulla, thyroid C cells, TSH- and FSH/LH-produting
cells of the anterior pituitary, A and B cells of pancreatic islets, in endocrine cells of the gastrointestinal tract and
the bronchial mucosa, and the prostate. Immunoreactivity determined by radioimmunoassay analysis revealed high secretoneurin
levels in the anterior and posterior pituitary and lower levels in pancreatic and thyroid tissue. A strong secretoneurin immunoreactivity
was also found in ganglion cells of the submucdsal and myenteric plexus of the gastrointestinal tract, and in ganglionic cells
of dorsal root ganglia, peripheral nerves, and ganglion cells of the adrenal medulla. Thus, secretoneurin may serve as a useful
marker of gangliocytic/neuronal differentiation. 相似文献
78.
Testosterone-regulated expression of enzymes involved in steroid and aromatic hydrocarbon catabolism in Comamonas testosteroni. 总被引:3,自引:0,他引:3
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)
The effect of testosterone as the sole carbon source on protein expression was analyzed in Comamonas testosteroni. Testosterone simultaneously induced the expression of steroid- and aromatic hydrocarbon-catabolizing enzymes and repressed one amino acid-degrading enzyme. It is suggested that steroids play a regulative role in catabolic enzyme synthesis during adaptive growth of C. testosteroni. 相似文献
79.
H. A. Schmid F. Schäfer H. Sann E. Simon 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1995,176(2):149-158
The responsiveness of spontaneously active neurons in the subfornical organ (SFO) of adult ducks to angiotensin II (ANGII), norepinephrine (NE), isoproterenol (Iso, -agonist), phenylephrine (Phe,
1-agonist) and clonidine (Clo,
2-agonist) was investigated in brain slices with extracellular recording technique. 64% (n=90) of the neurons increased their activity after superfusion with ANGII, the rest were unresponsive. Application of NE activated 10 and inhibited 8 neurons (n=22); the excitation being correlated with an excitatory ANGII responsiveness of the same neurons and the inhibition with the absence of an ANGII responsiveness. Iso activated 74% (n=58) and Clo inhibited 88% (n=16) of the investigated neurons. Phe did not have an effect on the majority (60%) of the neurons and produced both excitatory and inhibitory actions on the remaining cells. These results offer a plausible explanation for the dose dependent dipsogenic effect of Iso and the failure of NE to elicit dose dependent drinking, which can be explained by its dual, excitatory and inhibitory effect on SFO neurons. It is further concluded, that peripherally applied Iso exerts its dipsogenic action in high concentration by a direct excitatory effect on SFO neurons via the open blood brain barrier. Under physiological conditions, afferent neuronal input of still unknown origin might specifically modulate the activity of SFO neurons, because plasma concentrations of NE are probably not high enough to activate SFO neurons from the blood side of the blood brain barrier.Abbreviations
ACSF
artificial cerebrospinal fluid
-
ANGII
angiotensin II
-
Clo
clonidine
-
Iso
isoproterenol
-
NE
norepinephrine
-
NTS
nucleus of the solitary tract
-
Phe
phenylephrine
-
SFO
subfornical organ 相似文献
80.
HPLC-analysis of algal pigments: comparison of columns,column properties and eluents 总被引:1,自引:0,他引:1
The effects of columns (Nucleosil C18ODS, MZ-PAH, YMC-PACK C30), column properties (inner diameters of 4 mm, 3 mm and 2 mm, pore-width 10 nm and 30 nm) and eluents (methanol, acetonitrile,
acetone, water) were tested on the separation of algal pigments. The length of columns was 250 mm and particle size was 5
μm. Flow rates and gradients were adjusted to optimize peak separation; remaining chromatographic conditions were kept constant.
The resolution of chromatographic systems was tested with pigment standards and various algal cultures. Total flow rate and
retention times decreased with decreasing inner diameter, whereas pressure, sensitivity and peak-width increased. Pore width
had negligible effects on the chromatographic separation of pigments under the test conditions. Only with acetonitrile as
eluent were all the taxonomically important pigments resolved adequately: zeaxanthin (Cyanophyceae), lutein (Chlorophyceae),
fucoxanthin (Bacillariopyceae), alloxanthin (Cryptophyceae), peridinin (Dinophyceae). 相似文献